Skip to main content
SpringerLink
Log in

Pharmacology of Gasotransmitters (Nitric Oxide and Carbon Monoxide) and Their Action

  • Chapter
  • First Online:
Frontiers in Pharmacology of Neurotransmitters

Abstract

In the last decades, gasotransmitters have gained attention for their crucial role in pathophysiological and cellular functions. Gasotransmitters are gaseous mediators of the cellular signaling and biological responses from one end to the other. The isoform of these gaseous signaling molecules includes NO (nitric oxide), CO (carbon monoxide), and H2S (hydrogen sulphide), collectively called gasotransmitters. The diverse role of these gasotransmitters in cell and molecular biology as well as biochemical processing has been well validated through several scientific and clinical studies. The biosynthesis, interaction, and movement of gasotransmitters inside the cellular systems are critical especially in terms of their pharmacological response. These gaseous molecules are very toxic and hazardous to human health at higher concentrations but at lower levels they may be considered as therapeutic agents. They can easily diffuse through all the cell membrane and act on their targets for generating pharmacological responses. Due to its gaseous nature, the cellular interactions at the target sites are complex and make it a critical task for researchers to understand. The mode of action and molecular pathways are still under the exploratory phase. Apart from their toxic nature, there are several pharmacological activities such as cardioprotective, antihypertensive, smooth muscle relaxant, vasodilator, antithrombotic, antitumor, etc. that have been reported for these gaseous molecules. This gaseous family has become a promising area for multidisciplinary research in order to establish their importance in relation to disease and health. The perspective of these gasotransmitters is required to validate the clinical translational and future investigation following clear cut understanding of their pharmacological properties. This book chapter deals with the biosynthesis, pharmacological application and clinical utility of gaseous molecules mainly NO and CO.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AD:

Alzheimer’s Disease

ARDS:

Acute respiratory distress syndrome

BP:

Blood pressure

C/EBP:

CCAATT-enhancer-binding protein

CaM:

Calcium-binding messenger protein calmodulin

cGMP:

3,5-Cyclic guanosine monophosphate

CO:

Carbon monoxide

CO2 :

Carbon dioxide

CoHb:

Carboxyhemoglobin

COPD:

Chronic obstructive pulmonary disease

CORMs:

CO releasing molecules

CP:

Cisplatin

CVD:

Cardiovascular disease

CYT2E1:

Cytochrome P450 2E

DCM:

Dichloromethane

ED:

Erectile dysfunction

EDHF:

Endothelium-derived hyper polarizing factor

EDRF:

Endothelium-derived relaxing factor

ENOG:

European Network on Gasotransmitters

eNOS:

Endothelial NOS

ER:

Endoplasmic reticulum

GTN:

Glyceryltrinitrate

GTP:

Guanosine5-triphosphate

GTT:

Glucose tolerance test

H2S:

Hydrogen sulfide

Hb:

Hemoglobin

HIF:

Hypoxia inducible factor

HO:

Heme oxygenase

HO-1:

Heme oxygenase-1

HO-2:

Heme oxygenase-2

HUVECs:

Human umbilical vein endothelial cells

iNOS:

Inducible NOS

MAPK:

Mitogen activated protein kinases

MI:

Myocardial infarction

nNOS:

Neuronal NOS

NO:

Nitric oxide

NOS:

Nitric oxide synthase

O2 _ :

Peroxide radical

OH• :

Hydroxyl radical

ONOO:

Peroxynitrite

PAH:

Pulmonary arterial hypertension

PI3K:

Phosphatidyl inositol 3-kinase

PI3K:

Phosphatidylinositol-3 kinase

PKC:

Protein kinase C

PPARc:

Peroxisome proliferator-activated receptor-c

RAS:

Renin–angiotensin system

ROS:

Reactive oxygen species

S• :

Superoxide radical

sGC:

Soluble guanylatecyclase enzyme

SiRNA:

Small interfering RNA

TB:

Tuberculosis

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

VSMC:

Vascular smooth muscle cell

References

  • Abdelall EKA, Abdelhamid AO, Azouz AA (2017) Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids. Bioorg Med Chem Lett 27(18):4358–4369

    Article  CAS  Google Scholar 

  • Abraham NG, Kappas A (2008) Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev 60:79–127

    Article  CAS  Google Scholar 

  • Abraham NG, Jiang H, Balazy M, Goodman AI (2003) Methods for measurements of heme oxygenase (HO) isoforms-mediated synthesis of carbon monoxide and HO-1 and HO-2 proteins. Methods Mol Med 86:399–411

    CAS  Google Scholar 

  • Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, Patra CR, Reddy PN, Banerjee SK (2015) Hyperglycaemia enhances nitric oxide production in diabetes: a study from south Indian patients. PLoS One 10(4):e0125270

    Article  CAS  Google Scholar 

  • Akter F, Coghlan G, de Mel A (2016) Nitric oxide in paediatric respiratory disorders: novel interventions to address associated vascular phenomena? Ther Adv Cardiovasc Dis 10(4):256–270

    Article  CAS  Google Scholar 

  • Al Omar S, Salama H, Al HM, Al RH, Bunahia M, El Kasem W, Siddiqui FJ, Dilawar M, Yassin H, Masud F, Mohamed A, Mansour A (2016) Effect of early adjunctive use of oral sildenafil and inhaled nitric oxide on the outcome of pulmonary hypertension in newborn infants. A feasibility study. J Neonatal Perinatal Med 9(3):251–259

    Article  CAS  Google Scholar 

  • Alam J, Wicks C, Stewart D, Gong P, Touchard C, Otterbein L, Choi A, Burow M, Tou J.-s. (2000) Mechanism of Heme Oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of OF p38 kinase and Nrf2 transcription factor. J Biol Chem 275(36):27694–27702

    CAS  Google Scholar 

  • Allen TA, Root WS (1957) Partition of carbon monoxide and oxygen between air and whole blood of rats, dogs and men as affected by plasma pH. J Appl Physiol 10(2):186–190

    Article  CAS  Google Scholar 

  • Amsel SDJ, Kevin J, Soden KJ, Sielken RL Jr, Valdez-Flora C (2001) Observed versus predicted carboxyhemoglobin levels in cellulose triacetate workers exposed to methylene chloride. Am J Ind Med 40(2):180–191

    Article  CAS  Google Scholar 

  • Andreadou I, Iliodromitis EK, Rassaf T, Schulz R, Papapetropoulos A, Ferdinandy P (2015) The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol 172(6):1587–1606

    Article  CAS  Google Scholar 

  • Antosova M, Mokra D, Pepucha L, Plevkova J, Buday T, Sterusky M, Bencova A (2017) Physiology of nitric oxide in the respiratory system. Physiol Res 66(Supplementum 2):S159–S172

    Article  CAS  Google Scholar 

  • Archakov AI, Karuzina II, Petushkova N, Lisitsa AV, Zgoda V (2002) Production of carbon monoxide by cytochrome P450 during iron-dependent lipid peroxidation. Toxicol In Vitro 16(1):1–10

    Article  CAS  Google Scholar 

  • Arzumanian V, Stankevicius E, Laukeviciene A, Kevelaitis E (2003) Mechanisms of nitric oxide synthesis and action in cells. Medicina (Kaunas) 39(6):535–541

    Google Scholar 

  • Austin SA, Katusic ZS (2016) Loss of endothelial nitric oxide synthase promotes p25 generation and tau phosphorylation in a murine model of Alzheimer’s disease. Circ Res 119(10):1128–1134

    Article  CAS  Google Scholar 

  • Bagul A, Hosgood S, Kaushik M, Nicholson ML (2008) Carbon monoxide protects against ischemia-reperfusion injury in an experimental model of controlled nonheartbeating donor kidney. Transplantation 85(4):576–581

    Article  CAS  Google Scholar 

  • Baran CP, Zeigler MM, Tridandapani S, Marsh CB (2004) The role of ROS and RNS in regulating life and death of blood monocytes. Curr Pharm Des 10(8):855–866

    Article  CAS  Google Scholar 

  • Basudhar D, Somasundaram V, de Oliveira GA, Kesarwala A, Heinecke JL, Cheng RY, Glynn SA, Ambs S, Wink DA, Ridnour LA (2017) Nitric oxide Synthase-2-derived nitric oxide drives multiple pathways of breast Cancer progression. Antioxid Redox Signal 26(18):1044–1058

    Article  CAS  Google Scholar 

  • Bhat KH, Srivastava S, Kotturu SK, Ghosh S, Mukhopadhyay S (2017) The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production. Sci Rep 7:39706

    Article  CAS  Google Scholar 

  • Boehning D, Moon C, Sharma S, Hurt KJ, Hester LD, Ronnett GV, Shugar D, Snyder SH (2003) Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. Neuron 40(1):129–137

    Article  CAS  Google Scholar 

  • Bohlen HG (2015) Nitric oxide and the cardiovascular system. Compr Physiol 5(2):808–823

    Google Scholar 

  • Botros FT, Navar LG (2006) Interaction between endogenously produced carbon monoxide and nitric oxide in regulation of renal afferent arterioles. Am J Phys Heart Circ Phys 291(6):H2772–H2778

    CAS  Google Scholar 

  • Braverman J, Stanley SA (2017a) Nitric oxide modulates macrophage responses to Mycobacterium tuberculosis infection through activation of HIF-1alpha and repression of NF-kappaB. J Immunol 199(5):1805–1816

    Article  CAS  Google Scholar 

  • Braverman J, Stanley SA (2017b) Nitric oxide modulates macrophage responses to Mycobacterium tuberculosis infection through activation of HIF-1alpha and repression of NF-kappaB. J Immunol 199(5):1805–1816

    Article  CAS  Google Scholar 

  • Burnett AL (2006) The role of nitric oxide in erectile dysfunction: implications for medical therapy. J Clin Hypertens (Greenwich) 8(12 Suppl 4):53–62

    Article  CAS  Google Scholar 

  • Cartledge J, Minhas S, Eardley I (2001) The role of nitric oxide in penile erection. Expert Opin Pharmacother 2(1):95–107

    Article  CAS  Google Scholar 

  • Cepinskas G, Katada K, Bihari A, Potter RF (2008) Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. Am J Physiol Gastrointest Liver Physiol 294(1):G184–G191

    Article  CAS  Google Scholar 

  • Chen K, Maines MD (2000) Nitric oxide induces heme oxygenase-1 via mitogen-activated protein kinases ERK and p38. Cell Mol Biol (Noisy-le-Grand) 46(3):609–617

    CAS  Google Scholar 

  • Chen B, Guo L, Fan C, Bolisetty S, Joseph R, Wright MM, Agarwal A, George JF (2009) Carbon monoxide rescues Heme Oxygenase-1-deficient mice from arterial thrombosis in allogeneic aortic transplantation. Am J Pathol 175(1):422–429

    Article  CAS  Google Scholar 

  • Cheng Y, Rong J (2017) Therapeutic potential of Heme Oxygenase-1/carbon monoxide system against ischemia-reperfusion injury. Curr Pharm Des 23(26):3884–3898

    Article  CAS  Google Scholar 

  • Chin BY, Jiang G, Wegiel B, Wang HJ, MacDonald T, Zhang XC, Gallo D, Cszimadia E, Bach FH, Lee PJ, Otterbein LE (2007) Hypoxia-inducible factor 1α stabilization by carbon monoxide results in cytoprotective preconditioning. Proc Natl Acad Sci 104(12):5109–5114

    Article  CAS  Google Scholar 

  • Chinta KC, Saini V, Glasgow JN, Mazorodze JH, Rahman MA, Reddy D, Lancaster JR Jr, Steyn AJ (2016a) The emerging role of gasotransmitters in the pathogenesis of tuberculosis. Nitric Oxide 59:28–41

    Article  CAS  Google Scholar 

  • Chinta KC, Saini V, Glasgow JN, Mazorodze JH, Rahman MA, Reddy D, Lancaster JR Jr, Steyn AJ (2016b) The emerging role of gasotransmitters in the pathogenesis of tuberculosis. Nitric Oxide 59:28–41

    Article  CAS  Google Scholar 

  • Choi YK (2018) Role of carbon monoxide in neurovascular repair processing. Biomol Ther (Seoul) 26(2):93–100

    Article  CAS  Google Scholar 

  • Choi BM, Pae HO, Kim YM, Chung HT (2003) Nitric oxide-mediated cytoprotection of hepatocytes from glucose deprivation-induced cytotoxicity: involvement of heme oxygenase-1. Hepatology 37(4):810–823

    Article  CAS  Google Scholar 

  • Cifuentes D, Poittevin M, Bonnin P, Ngkelo A, Kubis N, Merkulova-Rainon T, Levy BI (2017) Inactivation of nitric oxide synthesis exacerbates the development of Alzheimer disease pathology in APPPS1 mice (amyloid precursor protein/Presenilin-1). Hypertension 70(3):613–623

    Article  CAS  Google Scholar 

  • Clark JE, Naughton P, Shurey S, Green CJ, Johnson TR, Mann BE, Foresti R, Motterlini R (2003) Cardioprotective actions by a water-soluble carbon monoxide-releasing molecule. Circ Res 93(2):e2–e8

    Article  CAS  Google Scholar 

  • Coburn RF (1970) The carbon monoxide body stores. Ann N Y Acad Sci U S A 174(1):11–22

    Article  CAS  Google Scholar 

  • Coburn RF, Mayers LB (1971) Myoglobin O2 tension determined from measurement of carboxymyoglobin in skeletal muscle. Am J Phys 220(1):66–74

    Article  CAS  Google Scholar 

  • Coburn RF, Blakemore WS, Forster RE (1963a) Endogenous carbon monoxide production in man. J Clin Invest 42:1172–1178

    Article  CAS  Google Scholar 

  • Coburn RF, Blakemore WS, Forster RE (1963b) Endogenous carbon monoxide production in man. J Clin Invest 42:1172–1178

    Article  CAS  Google Scholar 

  • Csongradi E, Juncos LA, Drummond HA, Vera T, Stec DE (2012) Role of carbon monoxide in kidney function: is a little carbon monoxide good for the kidney? Curr Pharm Biotechnol 13(6):819–826

    Article  CAS  Google Scholar 

  • Dallas ML, Scragg JL, Peers C (2009) Inhibition of L-type Ca(2+) channels by carbon monoxide. Adv Exp Med Biol 648:89–95

    Article  CAS  Google Scholar 

  • Dashwood MR, Crump A, Shi-Wen X, Loesch A (2011) Identification of neuronal nitric oxide synthase (nNOS) in human penis: a potential role of reduced neuronally-derived nitric oxide in erectile dysfunction. Curr Pharm Biotechnol 12(9):1316–1321

    Article  CAS  Google Scholar 

  • Divakaran S, Loscalzo J (2017) The role of nitroglycerin and other nitrogen oxides in cardiovascular therapeutics. J Am Coll Cardiol 70(19):2393–2410

    Article  CAS  Google Scholar 

  • Doroszko A, Dobrowolski P, Radziwon-Balicka A, Skomro R (2018) New insights into the role of oxidative stress in onset of cardiovascular disease. Oxidative Med Cell Longev 2018:9563831

    Article  Google Scholar 

  • Durante W, Christodoulides N, Cheng K, Peyton KJ, Sunahara RK, Schafer AI (1997) CAMP induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle. Am J Physiol 273(1 Pt 2):H317–H323

    CAS  Google Scholar 

  • Fabiani J-N, Achouh PE, Simonet S, Verbeuren TJ (2008) Carbon monoxide induces relaxation of human internal thoracic and radial arterial grafts. Interact Cardiovasc Thorac Surg 7(6):959–962

    Article  Google Scholar 

  • Fadel PJ (2017) Nitric oxide and cardiovascular regulation: beyond the endothelium. Hypertension 69(5):778–779

    Article  CAS  Google Scholar 

  • Farrugia G, Szurszewski JH (2014) Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology 147(2):303–313

    Article  CAS  Google Scholar 

  • Fleissner F, Thum T (2011) Critical role of the nitric oxide/reactive oxygen species balance in endothelial progenitor dysfunction. Antioxid Redox Signal 15(4):933–948

    Article  CAS  Google Scholar 

  • Fordjour PA, Wang Y, Shi Y, Agyemang K, Akinyi M, Zhang Q, Fan G (2015) Possible mechanisms of C-reactive protein mediated acute myocardial infarction. Eur J Pharmacol 760:72–80

    Article  CAS  Google Scholar 

  • Foresti R, Hammad J, Clark J, Johnson TR, Mann BE, Friebe A, Green C, Motterlini R (2004) Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing molecule. Br J Pharmacol 142(3):453–460

    Article  CAS  Google Scholar 

  • Forstermann U (2010) Nitric oxide and oxidative stress in vascular disease. Pflugers Arch 459(6):923–939

    Article  CAS  Google Scholar 

  • Forstermann U, Sessa WC (2012) (2012). Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837

    Article  CAS  Google Scholar 

  • Forstermann U, Xia N, Li H (2017) Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 120(4):713–735

    Article  CAS  Google Scholar 

  • Freitas A, Alves-Filho JC, Secco DD, Neto AF, Ferreira SH, Barja-Fidalgo C, Cunha FQ (2006) Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil rolling, adhesion and migration in acute inflammation. Br J Pharmacol 149(4):345–354

    Article  CAS  Google Scholar 

  • Fujimoto H, Ohno M, Ayabe S, Kobayashi H, Ishizaka N, Kimura H, Yoshida K-I, Nagai R (2004) Carbon monoxide protects against cardiac ischemia – reperfusion injury in vivo via MAPK and Akt – eNOS pathways. Arterioscler Thromb Vasc Biol 24(10):1848–1853

    Article  CAS  Google Scholar 

  • Fujisaki N, Kohama K, Nishimura T, Yamashita H, Ishikawa M, Kanematsu A, Yamada T, Lee S, Yumoto T, Tsukahara K, Kotani J, Nakao A (2016) Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats. Med Gas Res 6(3):122–129

    Article  CAS  Google Scholar 

  • Garcia-Mata C, Lamattina L (2013) Gasotransmitters are emerging as new guard cell signaling molecules and regulators of leaf gas exchange. Plant Sci 201-202:66–73

    Article  CAS  Google Scholar 

  • Hayashi S, Omata Y, Sakamoto H, Higashimoto Y, Hara T, Sagara Y, Noguchi M (2004) Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene. https://doi.org/10.1016/j.gene.2004.04.002

  • Heinemann SH, Hoshi T, Westerhausen M, Schiller A (2014) Carbon monoxide--physiology, detection and controlled release. Chem Commun (Camb) 50(28):3644–3660

    Article  CAS  Google Scholar 

  • Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT (2013) NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493(7434):674–678

    Article  CAS  Google Scholar 

  • Henningsson R, Alm P, Ekström P, Lundquist I (1999) Heme oxygenase and carbon monoxide: regulatory roles in islet hormone release - A biochemical, immunohistochemical, and confocal microscopic study. Diabetes 48(1):66–76

    Article  CAS  Google Scholar 

  • Hettiarachchi N, Dallas M, Al-Owais M, Griffiths H, Hooper N, Scragg J, Boyle J, Peers C (2014) Heme oxygenase-1 protects against Alzheimer’s amyloid-beta(1-42)-induced toxicity via carbon monoxide production. Cell Death Dis 5:e1569

    Article  CAS  Google Scholar 

  • Hou S, Xu R, Heinemann SH, Hoshi T (2008) The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.0800304105

  • Immenschuh S, Kietzmann T, Hinke V, Wiederhold M, Katz N, Muller-Eberhard U (1998) The rat heme oxygenase-1 gene is transcriptionally induced via the protein kinase A signaling pathway in rat hepatocyte cultures. Mol Pharmacol 53:483–491

    Article  CAS  Google Scholar 

  • Johnson TR, Mann BE, Clark J, Foresti R, Green C, Motterlini R (2003) Metal carbonyls: a new class of pharmaceuticals? Angew Chem Int Ed Engl 42(32):3722–3729

    Article  CAS  Google Scholar 

  • Johnson F, Johnson RA, Durante W, Jackson K, Stevenson BK, Peyton KJ (2006) Metabolic syndrome increases endogenous carbon monoxide production to promote endothelial dysfunction in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 290(3):R601–R608

    Article  CAS  Google Scholar 

  • Katusic ZS, Austin SA (2014) Endothelial nitric oxide: protector of a healthy mind. Eur Heart J 35(14):888–894

    Article  CAS  Google Scholar 

  • Keshet R, Erez A (2018) Arginine and the metabolic regulation of nitric oxide synthesis in cancer. Dis Model Mech 11(8):dmm033332

    Article  CAS  Google Scholar 

  • Kim HS, Loughran PA, Rao J, Billiar TR, Zuckerbraun BS (2008) Carbon monoxide activates NF-kappaB via ROS generation and Akt pathways to protect against cell death of hepatocytes. Am J Physiol Gastrointest Liver Physiol 295(1):G146–G152

    Article  CAS  Google Scholar 

  • Kobayashi A, Ishikawa K, Matsumoto H, Kimura S, Kamiyama Y, Maruyama Y (2007) Synergetic antioxidant and vasodilatory action of carbon monoxide in angiotensin II - induced cardiac hypertrophy. Hypertension 50(6):1040–1048

    Article  CAS  Google Scholar 

  • Kolluru GK, Shen X, Yuan S, Kevil CG (2017) Gasotransmitter heterocellular signaling. Antioxid Redox Signal 26(16):936–960

    Article  CAS  Google Scholar 

  • Kovacevic Z, Sahni S, Lok H, Davies MJ, Wink DA, Richardson DR (2017) Regulation and control of nitric oxide (NO) in macrophages: protecting the “professional killer cell” from its own cytotoxic arsenal via MRP1 and GSTP1. Biochim Biophys Acta Gen Subj. 1861(5 Pt A):995–999

    Article  CAS  Google Scholar 

  • Kubic VL, Anders MW (1978) Metabolism of dihalomethanes to carbon monoxide—III: studies on the mechanism of the reaction. Biochem Pharmacol 27(19):2349–2355

    Article  CAS  Google Scholar 

  • Lakkisto P, Kytö V, Forsten H, Siren J-M, Segersvärd H, Voipio-Pulkki L-M, Laine M, Pulkki K, Tikkanen I (2010) Heme oxygenase-1 and carbon monoxide promote neovascularization after myocardial infarction by modulating the expression of HIF-1α, SDF-1α and VEGF-B, vol 635, pp 156–164

    Google Scholar 

  • Lamon BD, Zhang FF, Puri N, Brodsky SV, Goligorsky MS, Nasjletti A (2009) Dual pathways of carbon monoxide–mediated vasoregulation. Circ Res 105(8):775–783

    Article  CAS  Google Scholar 

  • Lee T-S, Tsai H-L, Chau L-Y (2003) Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Δ12,14-prostaglandin J2. J Biol Chem 278:19325–19330

    Article  CAS  Google Scholar 

  • Lee M, Rey K, Besler K, Wang C, Choy J (2017) Immunobiology of nitric oxide and regulation of inducible nitric oxide synthase. Results Probl Cell Differ 62:181–207

    Article  CAS  Google Scholar 

  • Leffler CW, Nasjletti A, Yu C, Johnson RA, Fedinec AL, Walker N (1999) Carbon monoxide and cerebral microvascular tone in newborn pigs. Am J Phys Heart Circ Phys 276(5):H1641–H1646

    CAS  Google Scholar 

  • Li VG, Sacerdoti D, Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck J, Abraham NG (2005) Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells. Antioxid Redox Signal. https://doi.org/10.1089/ars.2005.7.704

  • Li A, Xi Q, Umstot ES, Bellner L, Schwartzman ML, Jaggar JH, Leffler CW (2008) Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle cell KCa channels. Circ Res 102(2):234–241

    Article  CAS  Google Scholar 

  • Li L, Hsu A, Moore PK (2009) Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation—a tale of three gases! Pharmacol Ther. https://doi.org/10.1016/j.pharmthera.2009.05.005

  • Li H, Horke S, Forstermann U (2014) Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 237(1):208–219

    Article  CAS  Google Scholar 

  • Lin HH, Lai SC, Chau LY (2011) Heme oxygenase-1/carbon monoxide induces vascular endothelial growth factor expression via p38 kinase-dependent activation of Sp1. J Biol Chem 286(5):3829–3838

    Article  CAS  Google Scholar 

  • Ling K, Men F, Wang W-C, Zhou Y-Q, Zhang H-W, Ye D-W (2017) Carbon monoxide and its controlled release: therapeutic application, detection, and development of carbon monoxide releasing molecules (CORMs). J Med Chem. https://doi.org/10.1021/acs.jmedchem.6b01153

  • Lowenstein CJ, Dinerman JL, Snyder SH (1994) Nitric oxide: a physiologic messenger. Ann Intern Med 120(3):227–237

    Article  CAS  Google Scholar 

  • Luo S, Lei H, Qin H, Xia Y (2014) Molecular mechanisms of endothelial NO synthase uncoupling. Curr Pharm Des 20(22):3548–3553

    Article  CAS  Google Scholar 

  • MacMicking J, Xie QW, Nathan C (1997a) Nitric oxide and macrophage function. Annu Rev Immunol 15:323–350

    Article  CAS  Google Scholar 

  • MacMicking J, Xie QW, Nathan C (1997b) Nitric oxide and macrophage function. Annu Rev Immunol 15:323–350

    Article  CAS  Google Scholar 

  • McCoubrey WK Jr, Huang TJ, Maines MD (1997) Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247(2):725–732

    Article  CAS  Google Scholar 

  • Miller MR, Megson IL (2007) Recent developments in nitric oxide donor drugs. Br J Pharmacol 151(3):305–321

    Article  CAS  Google Scholar 

  • Mir JM, Maurya R (2018) A gentle introduction to gasotransmitters with special reference to nitric oxide: biological and chemical implications. Rev Inorg Chem 38(4):193–220

    Article  CAS  Google Scholar 

  • Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329(27):2002–2012

    Article  CAS  Google Scholar 

  • Motterlini R, Foresti R (2017) Biological signaling by carbon monoxide and carbon monoxide-releasing molecules. Am J Physiol Cell Physiol 312(3):C302–C313

    Article  Google Scholar 

  • Motterlini R, Otterbein LE (2010) The therapeutic potential of carbon monoxide. Nat Rev Drug Discov 9(9):728–743

    Article  CAS  Google Scholar 

  • Munzel T, Daiber A (2018) Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to organic nitrates as nitric oxide donors? Vasc Pharmacol 102:1–10

    Article  CAS  Google Scholar 

  • Nagpure BV, Bian JS (2016) Interaction of hydrogen sulfide with nitric oxide in the cardiovascular system. Oxidative Med Cell Longev 2016:6904327

    Article  CAS  Google Scholar 

  • Nakao A, Huang C-S, Stolz DB, Wang Y, Franks J, Tochigi N, R Billiar T, Toyoda Y, Tzeng E, R McCurry K (2011) Ex vivo carbon monoxide delivery inhibits intimal hyperplasia in arterialized vein grafts. Cardiovasc Res. https://doi.org/10.1093/cvr/cvq298

  • Naseem KM (2005) The role of nitric oxide in cardiovascular diseases. Mol Asp Med 26(1–2):33–65

    Article  CAS  Google Scholar 

  • Ndisang JF, Tabien HEN, Wang R (2004) Carbon monoxide and hypertension. J Hypertens 22(6):1057–1074

    Article  CAS  Google Scholar 

  • Neilly PJ, Kirk SJ, Gardiner KR, Rowlands BJ (1994) The L-arginine/nitric oxide pathway--biological properties and therapeutic applications. Ulster Med J 63(2):193–200

    CAS  Google Scholar 

  • Nizamutdinova IT, Kim YM, Kim HJ, Seo HG, Lee JH, Chang KC (2009) Carbon monoxide (from CORM-2) inhibits high glucose-induced ICAM-1 expression via AMP-activated protein kinase and PPAR-γ activations in endothelial cells. Atherosclerosis 207(2):405–411

    Article  CAS  Google Scholar 

  • Nobre LS, Seixas JD, Romão CC, Saraiva LM (2007) Antimicrobial action of carbon monoxide-releasing compounds. Antimicrob Agents Chemother 51(12):4303–4307

    Article  CAS  Google Scholar 

  • Okuyama H, Yonetani M, Uetani Y, Nakamura H (2001) End-tidal carbon monoxide is predictive for neonatal non-hemolytic hyperbilirubinemia. Pediatr Int 43(4):329–333

    Article  CAS  Google Scholar 

  • Olah G, Modis K, Toro G, Hellmich MR, Szczesny B, Szabo C (2018) Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation. Biochem Pharmacol 149:186–204

    Article  CAS  Google Scholar 

  • Omar SA, Webb AJ, Lundberg JO, Weitzberg E (2016) Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J Intern Med 279(4):315–336

    Article  CAS  Google Scholar 

  • Owens EO (2010) Endogenous carbon monoxide production in disease. Clin Biochem 43(15):1183–1188

    Article  CAS  Google Scholar 

  • Pamplona A, Ferreira A, Balla J, Jeney V, Balla G, Epiphanio S, Chora Â, Rodrigues CD, Grégoire I, Cunha-Rodrigues M, Portugal S, P Soares M, Mota M (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med. 13(6):703–710

    Article  CAS  Google Scholar 

  • Papapetropoulos A, Foresti R, Ferdinandy P (2015) Pharmacology of the ‘gasotransmitters’ NO, CO and H2S: translational opportunities. Br J Pharmacol 172(6):1395–1396

    Article  CAS  Google Scholar 

  • Paredi P, Biernacki W, Invernizzi G, Kharitonov SA, Barnes PJ (1999) Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: A new test for monitoring the disease? Chest 116(4):1007–1011

    Article  CAS  Google Scholar 

  • Paul BD, Snyder SH (2018a) Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. Biochem Pharmacol 149:101–109

    Article  CAS  Google Scholar 

  • Paul BD, Snyder SH (2018b) Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. Biochem Pharmacol 149:101–109

    Article  CAS  Google Scholar 

  • Piazza M, Dieckmann T, Guillemette JG (2018) Investigation of the structure and dynamic of calmodulin-nitric oxide synthase complexes using NMR spectroscopy. Front Biosci (Landmark Ed) 23:1902–1922

    Article  CAS  Google Scholar 

  • Pitsikas N (2015) The role of nitric oxide in the object recognition memory. Behav Brain Res 285:200–207

    Article  CAS  Google Scholar 

  • Polhemus DJ, Lefer DJ (2014) Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res 114(4):730–737

    Article  CAS  Google Scholar 

  • Poulos TL, Li H (2017) Nitric oxide synthase and structure-based inhibitor design. Nitric Oxide 63:68–77

    Article  CAS  Google Scholar 

  • Queiroga C, Almeida A, Alves P, Brenner C, Vieira H (2011) Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC Cell Biol 12:10

    Article  CAS  Google Scholar 

  • Quillon A, Fromy B, Debret R (2015) Endothelium microenvironment sensing leading to nitric oxide mediated vasodilation: a review of nervous and biomechanical signals. Nitric Oxide 45:20–26

    Article  CAS  Google Scholar 

  • Raman K, Barbato JE, Ifedigbo E, Ozanich BA, Zenati M, Otterbein L, Tzeng E (2006) Inhaled carbon monoxide inhibits intimal hyperplasia and provides added benefit with nitric oxide. J Vasc Surg. 44(1):151–158

    Article  Google Scholar 

  • Ramlawi B, Scott JR, Feng J, Mieno S, Raman KG, Gallo D, Csizmadia E, Yoke CB, Bach FH, Otterbein LE, Sellke FW (2007) Inhaled carbon monoxide prevents graft-induced intimal hyperplasia in swine. J Surg Res 138(1):121–127

    Article  CAS  Google Scholar 

  • Riddell DR, Owen JS (1999) Nitric oxide and platelet aggregation. Vitam Horm 57:25–48

    Article  CAS  Google Scholar 

  • Rochette L, Lorin J, Zeller M, Guilland JC, Lorgis L, Cottin Y, Vergely C (2013) Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? Pharmacol Ther 140(3):239–257

    Article  CAS  Google Scholar 

  • Ryter SW, Choi AM (2013) Carbon monoxide: present and future indications for a medical gas. Korean J Intern Med 28(2):123–140

    Article  CAS  Google Scholar 

  • Shahrbaf MA, Mahjoob MP, Khaheshi I, Akbarzadeh MA, Barkhordari E, Naderian M, Tajrishi FZ (2018) The role of air pollution on ST-elevation myocardial infarction: A narrative mini review. Futur Cardiol 14(4):301–306

    Article  CAS  Google Scholar 

  • Shefa U, Yeo SG, Kim MS, Song IO, Jung J, Jeong NY, Huh Y (2017) Role of gasotransmitters in oxidative stresses, neuroinflammation, and neuronal repair. Biomed Res Int. https://doi.org/10.1155/2017/1689341. Epub 2017 Mar 12

  • Simon T, Anegon I, Blancou P (2011) Heme oxygenase and carbon monoxide as an immunotherapeutic approach in transplantation and cancer. Immunotherapy 3(4 Suppl):15–18

    Article  CAS  Google Scholar 

  • Sjostrand T (1952) The formation of carbon monoxide by the decomposition of haemoglobin in vivo. Acta Physiol Scand 26(4):338–344

    Article  CAS  Google Scholar 

  • Socco S, Bovee RC, Palczewski MB, Hickok JR, Thomas DD (2017) Epigenetics: the third pillar of nitric oxide signaling. Pharmacol Res 121:52–58

    Article  CAS  Google Scholar 

  • Stein A, Guo Y, Tan W, Wu W-J, Zhu X, Li Q, Luo C, Dawn B, Johnson TR, Motterlini R, Bolli R (2005) Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. J Mol Cell Cardiol 38(1):127–134

    Article  CAS  Google Scholar 

  • Stevenson DK, Vreman HJ, Oh W, Fanaroff AA, Wright LL, Lemons JA, Verter J, Shankaran S, Tyson JE, Korones SB et al (1994) Bilirubin production in healthy term infants as measured by carbon monoxide in breath. Clin Chem 40(10):1934–1939

    Article  CAS  Google Scholar 

  • Stewart RD, Fisher TN, Hosko MJ, Peterson JE, Baretta ED, Dodd HC (1972) Carboxyhemoglobin elevation after exposure to dichloromethane. Science 176(4032):295–296

    Article  CAS  Google Scholar 

  • Sukmansky OI, Reutov VP (2016) Gasotransmitters: physiological role and involvement in the pathogenesis of the diseases. Usp Fiziol Nauk 47(3):30–58

    CAS  Google Scholar 

  • Szabo C (2010) Gaseotransmitters: new frontiers for translational science. Sci Transl Med 2(59):59ps54. https://doi.org/10.1126/scitranslmed.3000721

    Article  CAS  Google Scholar 

  • Takehito T, Yoshifumi M (1988) Metabolism of dichloromethane and the subsequent binding of its product, carbon monoxide, to cytochrome P-450 in perfused rat liver. Toxicol Lett 40(1):93–96

    Article  Google Scholar 

  • Tayem Y, Johnson TR, Mann BE, Green CJ, Motterlini R (2006) Protection against cisplatin-induced nephrotoxicity by a carbon monoxide-releasing molecule. Am J Physiol Renal Physiol 290(4):F789–F794

    Article  CAS  Google Scholar 

  • Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61(2):748–755

    Article  CAS  Google Scholar 

  • Terry C, Clikeman JA, Hoidal JR, Callahan KS (1999) TNF-alpha and IL-1alpha induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. Am J Physiol 276(5):H1493–H1501

    CAS  Google Scholar 

  • Thom SR (1990) Carbon monoxide-mediated brain lipid peroxidation in the rat. J Appl Physiol 68(3):997–1003

    Article  CAS  Google Scholar 

  • Traub O, Van Bibber R (1995) Role of nitric oxide in insulin-dependent diabetes mellitus-related vascular complications. West J Med 162(5):439–445

    CAS  Google Scholar 

  • Truss NJ, Warner T (2011a) Gasotransmitters and platelets. Pharmacol Ther 132(2):196–203

    Article  CAS  Google Scholar 

  • Truss NJ, Warner TD (2011b) Gasotransmitters and platelets. Pharmacol Ther 132(2):196–203

    Article  CAS  Google Scholar 

  • Untereiner A, Wu L, Wang R (2012) The role of carbon monoxide as a gasotransmitter. In: Hermann A, Sitdikova G, Weiger T (eds) Gasotransmitters: physiology and pathophysiology, pp 37–70

    Chapter  Google Scholar 

  • Urquhart P, Rosignoli G, Cooper D, Motterlini R, Perretti M (2007) Carbon monoxide-releasing molecules modulate leukocyte-endothelial interactions under flow. J Pharmacol Exp Ther 321(2):656–662

    Article  CAS  Google Scholar 

  • van den Born JC, Hammes HP, Greffrath W, van Goor H, Hillebrands JL, DFG GRK International Research Training Group 1874 Diabetic Microvascular Complications (DIAMICOM) (2016) Gasotransmitters in vascular complications of diabetes. Diabetes 65(2):331–345

    Article  CAS  Google Scholar 

  • Van Landeghem L, Laleman W, Van der Elst I, Zeegers M, Van Pelt J, Cassiman D, Nevens F (2009) Carbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulates the vascular tone in cirrhotic rat liver. Liver Int 29(5):650–660

    Article  CAS  Google Scholar 

  • Vanhoutte PM, Gao Y (2013) Beta blockers, nitric oxide, and cardiovascular disease. Curr Opin Pharmacol 13(2):265–273

    Article  CAS  Google Scholar 

  • Vannacci A, Di Felice A, Giannini L, Marzocca C, Pierpaolo S, Zagli G, Masini E, Mannaioni PF (2004) The effect of carbon monoxide releasing molocule on the immunological activation of guinea-pig mast cells and human basophils. Inflamm Res; 53 Suppl 1:S9–S10

    Google Scholar 

  • Varadi J, Lekli I, Juhasz B, Bácskay I, Szabo G, Gesztelyi R, Szendrei L, Varga E, Bak I, Foresti R, Motterlini R, Tosaki A (2007) Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery, vol 80, pp 1619–1626

    Google Scholar 

  • Venketaraman V, Talaue MT, Dayaram YK, Peteroy-Kelly MA, Bu W, Connell ND (2003) Nitric oxide regulation of L-arginine uptake in murine and human macrophages. Tuberculosis (Edinb) 83(5):311–318

    Article  Google Scholar 

  • Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon monoxide: a putative neural messenger. Science 259(5093):381–384

    Article  CAS  Google Scholar 

  • Von Burg R (1999) Carbon monoxide. J Appl Toxicol 19(5):379–386

    Article  Google Scholar 

  • Wagner CT, Durante W, Christodoulides N, Hellums JD, Schafer AI (1997) Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. J Clin Invest 100(3):589–596

    Article  CAS  Google Scholar 

  • Wallace JL, Ianaro A, Flannigan KL, Cirino G (2015) Gaseous mediators in resolution of inflammation. Semin Immunol 27(3):227–233

    Article  CAS  Google Scholar 

  • Wang R (1998) Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor. Can J Physiol Pharmacol 76(1):1–15

    Article  Google Scholar 

  • Wang R (2014) Gasotransmitters: growing pains and joys. Trends Biochem Sci 39(5):227–232

    Article  CAS  Google Scholar 

  • Wang R, Wu L, Wang Z (1997) The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells. Pflugers Arch 434(3):285–291

    Article  CAS  Google Scholar 

  • Wang R, Wang Z, Wu L, Hanna ST, Peterson-Wakeman R (2001) Reduced vasorelaxant effect of carbon monoxide in diabetes and the underlying mechanisms. Diabetes 50(1):166–174

    Article  CAS  Google Scholar 

  • Wang Z, Wu Y, Zhang S, Zhao Y, Yin X, Wang W, Ma X, Liu H (2019) The role of NO-cGMP pathway inhibition in vascular endothelial-dependent smooth muscle relaxation disorder of AT1-AA positive rats: protective effects of adiponectin. Nitric Oxide 87:10–22

    Article  CAS  Google Scholar 

  • Wegiel B, Gallo DJ, Raman KG, Karlsson JM, Ozanich B, Chin BY, Tzeng E, Ahmad S, Ahmed A, Baty CJ, Otterbein LE (2010) Nitric oxide–dependent bone marrow progenitor mobilization by carbon monoxide enhances endothelial repair after vascular injury. Circulation 121(4):537–548

    Article  CAS  Google Scholar 

  • Wegiel B, Gallo D, Csizmadia E, Harris C, Belcher J, Vercellotti GM, Penacho N, Seth P, Sukhatme V, Ahmed A, Pandolfi PP, Helczynski L, Bjartell A, Persson JL, Otterbein LE (2013) Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. Cancer Res 73(23):7009–7021

    Article  CAS  Google Scholar 

  • Wen L, Feil S, Wolters M, Thunemann M, Regler F, Schmidt K, Friebe A, Olbrich M, Langer H, Gawaz M, de Wit C, Feil R (2018) A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis. Nat Commun 9(1):4301

    Article  CAS  Google Scholar 

  • Wobst J, Kessler T, Dang TA, Erdmann J, Schunkert H (2015) Role of sGC-dependent NO signalling and myocardial infarction risk. J Mol Med (Berl) 93(4):383–394

    Article  CAS  Google Scholar 

  • Wu L, Wang R (2005a) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57(4):585–630

    Article  CAS  Google Scholar 

  • Wu L, Wang R (2005b) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57(4):585–630

    Article  CAS  Google Scholar 

  • Wu L, Wang R (2006) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57(4):585–630

    Article  CAS  Google Scholar 

  • Xi Q, Tcheranova D, Parfenova H, Horowitz B, Leffler CW, Jaggar JH (2004) Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of alpha-subunits. Am J Physiol Heart Circ Physiol 286(2):H610–H618

    Article  CAS  Google Scholar 

  • Yarlagadda K, Hassani J, Foote IP, Markowitz J (2017) The role of nitric oxide in melanoma. Biochim Biophys Acta Rev Cancer 1868(2):500–509

    Article  CAS  Google Scholar 

  • Zang Y, Popat KC, Reynolds MM (2018) Nitric oxide-mediated fibrinogen deposition prevents platelet adhesion and activation. Biointerphases 13(6):06E403

    Article  CAS  Google Scholar 

  • Zhao Y, Vanhoutte PM, Leung SW (2015) Vascular nitric oxide: beyond eNOS. J Pharmacol Sci 129(2):83–94

    Article  CAS  Google Scholar 

  • Zheng L, Zhou Z, Lin L, Alber S, Watkins S, Kaminski N, Choi AMK, Morse D (2009) Carbon monoxide modulates α–smooth muscle actin and small proline rich-1a expression in fibrosis. Am J Respir Cell Mol Biol 41(1):85–92

    Article  CAS  Google Scholar 

  • Zhou Z, Song R, Fattman C, Greenhill S, Alber S, Oury T, Choi A, Morse D (2005) Carbon monoxide suppresses bleomycin-induced lung fibrosis, vol 166, pp 27–37

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India

    Rohitas Deshmukh & Ranjit K. Harwansh

  2. Molecular Biology Division, National Institute of Malarial Research (NIMR), Dwarka, Delhi, India

    Nabamita Bandyopadhyay

  3. Faculty of Pharmacy, Naraina Vidya Peeth Group of Institutions, Kanpur, Uttar Pradesh, India

    Shantanu Bandopadhyay

  4. Department of Pharmacology, Central University of Punjab, Bathinda, Punjab, India

    Puneet Kumar

  5. Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India

    Puneet Kumar

Authors
  1. Rohitas Deshmukh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranjit K. Harwansh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nabamita Bandyopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shantanu Bandopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Puneet Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Central University of Punjab, Bathinda, Punjab, India

    Puneet Kumar

  2. Department of Pharmaceutical Sciences Faculty of Pharmacy, Philadelphia University, Amman, Jordan

    Pran Kishore Deb

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Deshmukh, R., Harwansh, R.K., Bandyopadhyay, N., Bandopadhyay, S., Kumar, P. (2020). Pharmacology of Gasotransmitters (Nitric Oxide and Carbon Monoxide) and Their Action. In: Kumar, P., Deb, P.K. (eds) Frontiers in Pharmacology of Neurotransmitters. Springer, Singapore. https://doi.org/10.1007/978-981-15-3556-7_17

Download citation

Publish with us

Policies and ethics

Search

Navigation