Skip to main content
SpringerLink
Log in

Pulmonary Vascular Physiology and Pathophysiology

  • Reference work entry
  • First Online:
PanVascular Medicine

  • 250 Accesses

Abstract

The unique physiologic properties of the pulmonary vasculature allow it to play a highly active role in optimizing gas exchange. The process of gas exchange requires both alveolar ventilation and capillary perfusion; however, in certain disease states, including pneumonia and atelectasis, the distribution of either ventilation or perfusion is altered, creating a situation of ventilation-perfusion (V/Q) mismatch. The physiologic property of hypoxic pulmonary vasoconstriction (HPV) allows the pulmonary vasculature to partially correct for this mismatch by shunting blood away from poorly ventilated alveoli. However, although HPV improves oxygenation acutely, when uncontrolled or uncoupled, this adaptive response can have devastating consequences including vascular remodeling and ultimately pulmonary hypertension (PH). Additionally, in order for efficient gas exchange to take place, the body has evolved an extremely thin blood-gas barrier with a vast surface area; however, these structural properties also pose an additional challenge to the vasculature in terms of maintaining barrier function. The integrity of the endothelial monolayer is critical to fluid balance across the lung, and its disruption can lead to vascular leak, impaired gas exchange, and ultimately multisystem organ failure, characteristic of the acute respiratory distress syndrome (ARDS). Lastly, the proximity of the lung vasculature to the outside environment makes the lung highly susceptible to inflammatory processes caused by inhalation of microorganisms and inorganic particulate matter. Thus, the pulmonary endothelium plays a key role in modulating inflammation and hemostasis in order to contain infections, repair damaged vasculature, and prevent thrombosis. In this chapter we will describe the physiologic mechanisms underlying the contribution of the pulmonary vasculature to the processes of V/Q matching, barrier maintenance, inflammation, and hemostasis.

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 649.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
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

AA:

Arachidonic Acid

AJ:

Adherens Junction

ALI:

Acute Lung Injury

APC:

Activated Protein C

ARDS:

Acute Respiratory Distress Syndrome

ATP:

Adenosine Triphosphate

CaM:

Calmodulin

Cav-1:

Caveolin-1

CD:

Cluster Differentiation

DIC:

Disseminated Intravascular Coagulation

ECM:

Extracellular Matrix

eNOS:

Endothelial Nitric Oxide Synthase

EPCR:

Endothelial Protein C Receptor

ETC:

Electron Transport Chain

FA:

Focal Adhesion

GJ:

Gap Junction

H2O2 :

Hydrogen Peroxide

HIF:

Hypoxia-Inducible Factor

HPV:

Hypoxic Pulmonary Vasoconstriction

I-CAM:

Intercellular Adhesion Molecule

JAM:

Junctional Adhesion Molecule

K2P :

Two-Pore Potassium Channel

KCa :

Calcium-Sensitive Potassium Channel

Kf,c :

Filtration Coefficient

Kir :

Inward Rectifier Potassium Channel

KO:

Knockout

Kv :

Voltage-Gated Potassium Channel

IFN:

Interferon

IL:

Interleukin

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated Protein Kinase

MLC:

Myosin Light Chain

MLCK:

Myosin Light Chain Kinase

nmMLCK:

Nonmuscle Myosin Light Chain Kinase

NO:

Nitric Oxide

PA :

Alveolar Pressure

Pa :

Arterial Pressure

PAO2 :

Alveolar Partial Pressure of Oxygen

PAI-1:

Plasminogen Activator Inhibitor 1

PAMP:

Pathogen-Associated Molecular Pattern

PASMC:

Pulmonary Artery Smooth Muscle Cell

PE-CAM:

Platelet Endothelial Cellular Adhesion Molecule

PGI2 :

Prostacyclin

PH:

Pulmonary Hypertension

pMLC:

Phosphorylated Myosin Light Chain

Pv :

Venous Pressure

ROS:

Reactive Oxygen Species

S1P:

Sphingosine 1-Phosphate

SNP:

Single Nucleotide Polymorphism

SOD:

Superoxide Dismutase

TF:

Tissue Factor

TFPI:

Tissue Factor Pathway Inhibitor

TJ:

Tight Junction

TNF:

Tumor Necrosis Factor

tPA:

Tissue Plasminogen Activator

TLR4:

Toll-Like Receptor 4

V/Q:

Ventilation/Perfusion

V-CAM:

Vascular Cellular Adhesion Molecule

VDCC:

Voltage-Dependent Calcium Channel

VEGF:

Vascular Endothelial Growth Factor

vWF:

von Willebrand Factor

References

  • Albelda SM, Smith CW, Ward PA (1994) Adhesion molecules and inflammatory injury. FASEB J 8(8):504–512

    CAS  PubMed  Google Scholar 

  • Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E (1999) Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arterioscler Thromb Vasc Biol 19(10):2286–2297

    Article  CAS  PubMed  Google Scholar 

  • Archer SL, Will JA, Weir EK (1986) Redox status in the control of pulmonary vascular tone. Herz 11(3):127–141

    CAS  PubMed  Google Scholar 

  • Archer SL, Nelson DP, Weir EK (1989/1985) Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung. J Appl Physiol 67(5):1903–1911

    Google Scholar 

  • Archer SL, Huang J, Henry T, Peterson D, Weir EK (1993) A redox-based O2 sensor in rat pulmonary vasculature. Circ Res 73(6):1100–1112

    Article  CAS  PubMed  Google Scholar 

  • Archer SL, Hampl V, Nelson DP, Sidney E, Peterson DA, Weir EK (1995) Dithionite increases radical formation and decreases vasoconstriction in the lung. Evidence that dithionite does not mimic alveolar hypoxia. Circ Res 77(1):174–181

    Article  CAS  PubMed  Google Scholar 

  • Archer SL, Souil E, Dinh-Xuan AT, Schremmer B, Mercier JC, El Yaagoubi A, Nguyen-Huu L, Reeve HL, Hampl V (1998) Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J Clin Invest 101(11):2319–2330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Archer SL, Reeve HL, Michelakis E, Puttagunta L, Waite R, Nelson DP, Dinauer MC, Weir EK (1999) O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc Natl Acad Sci U S A 96(14):7944–7949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Archer SL, London B, Hampl V, Wu X, Nsair A, Puttagunta L, Hashimoto K, Waite RE, Michelakis ED (2001) Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage-gated potassium channel Kv1.5. FASEB J 15(10):1801–1803

    CAS  PubMed  Google Scholar 

  • Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK (2008) Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1 alpha-Kv1.5 O2-Sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 294(2):H570–H578

    Article  CAS  PubMed  Google Scholar 

  • Becker PM, Verin AD, Booth MA, Liu F, Birukova A, Garcia JG (2001) Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 281(6):L1500–L1511

    CAS  PubMed  Google Scholar 

  • Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA (1986) Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A 83(12):4533–4537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bindslev L, Jolin A, Hedenstierna G, Baehrendtz S, Santesson J (1985) Hypoxic pulmonary vasoconstriction in the human lung: effect of repeated hypoxic challenges during anesthesia. Anesthesiology 62(5):621–625

    Article  CAS  PubMed  Google Scholar 

  • Birukov KG, Csortos C, Marzilli L, Dudek S, Ma SF, Bresnick AR, Verin AD, Cotter RJ, Garcia JG (2001) Differential regulation of alternatively spliced endothelial cell myosin light chain kinase isoforms by p60(Src). J Biol Chem 276(11):8567–8573

    Article  CAS  PubMed  Google Scholar 

  • Bombeli T, Mueller M, Haeberli A (1997) Anticoagulant properties of the vascular endothelium. Thromb Haemost 77(3):408–423

    CAS  PubMed  Google Scholar 

  • Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP (1988) The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood 71(2):335–343

    CAS  PubMed  Google Scholar 

  • Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P (2003) Heterozygous deficiency of hypoxia-inducible factor-2 alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 111(10):1519–1527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF, Inflammation and Host Response to Injury Large Scale Collaborative Research Program (2005) A network-based analysis of systemic inflammation in humans. Nature 437(7061):1032–1037

    Article  CAS  PubMed  Google Scholar 

  • Chiang E, Wang T, Garcia JGN (2011) Acute lung injury: the injured lung endothelium, therapeutic strategies for barrier protection, and vascular biomarkers. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 197–222

    Chapter  Google Scholar 

  • Christie JD, Ma SF, Aplenc R, Li M, Lanken PN, Shah CV, Fuchs B, Albelda SM, Flores C, Garcia JG (2008) Variation in the myosin light chain kinase gene is associated with development of acute lung injury after major trauma. Crit Care Med 36(10):2794–2800

    Article  PubMed  Google Scholar 

  • Corada M, Mariotti M, Thurston G, Smith K, Kunkel R, Brockhaus M, Lampugnani MG, Martin-Padura I, Stoppacciaro A, Ruco L, McDonald DM, Ward PA, Dejana E (1999) Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci U S A 96(17):9815–9820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Couet J, Belanger MM, Roussel E, Drolet MC (2001) Cell biology of caveolae and caveolin. Adv Drug Deliv Rev 49(3):223–235

    Article  CAS  PubMed  Google Scholar 

  • Crawley JTB, Gonzales-Porras JR, Lane DA (2011) The coagulation cascade and its regulation. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 357–370

    Chapter  Google Scholar 

  • Curtis TM, McKeown-Longo PJ, Vincent PA, Homan SM, Wheatley EM, Saba TM (1995) Fibronectin attenuates increased endothelial monolayer permeability after RGD peptide, anti-alpha 5 beta 1, or TNF-alpha exposure. Am J Physiol 269(2 Pt 1):L248–L260

    CAS  PubMed  Google Scholar 

  • De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA, Shin WS, Liao JK (1995) Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96(1):60–68

    Article  PubMed  PubMed Central  Google Scholar 

  • Dejana E, Giampietro C (2012) Vascular endothelial-cadherin and vascular stability. Curr Opin Hematol 19(3):218–223

    Article  CAS  PubMed  Google Scholar 

  • Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121(Pt 13):2115–2122

    Article  CAS  PubMed  Google Scholar 

  • Dietzen DJ, Hastings WR, Lublin DM (1995) Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J Biol Chem 270(12):6838–6842

    Article  CAS  PubMed  Google Scholar 

  • Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293(5539):2449–2452

    Article  CAS  PubMed  Google Scholar 

  • Dudek SM, Garcia JG (2001) Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol 91(4):1487–1500

    CAS  PubMed  Google Scholar 

  • Dudek SM, Jacobson JR, Chiang ET, Birukov KG, Wang P, Zhan X, Garcia JG (2004) Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase. J Biol Chem 279(23):24692–24700

    Article  CAS  PubMed  Google Scholar 

  • Effros RM, Parker JC (2009) Pulmonary vascular heterogeneity and the Starling hypothesis. Microvasc Res 78(1):71–77

    Article  PubMed  Google Scholar 

  • Esmon CT (1987) The regulation of natural anticoagulant pathways. Science 235(4794):1348–1352

    Article  CAS  PubMed  Google Scholar 

  • Esmon CT (1992) The protein C anticoagulant pathway. Arterioscler Thromb 12(2):135–145

    Article  CAS  PubMed  Google Scholar 

  • Félétou M, Vanhoutte PM (2006) Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291(3):H985–H1002

    Article  PubMed  CAS  Google Scholar 

  • Firth A, Yuan J (2011) Ion channels and transporters in the pulmonary vasculature: a focus on smooth muscle. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 223–244

    Chapter  Google Scholar 

  • Fischer S, Wobben M, Marti HH, Renz D, Schaper W (2002) Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res 63(1):70–80

    Article  CAS  PubMed  Google Scholar 

  • Flores C, Ma SF, Maresso K, Ober C, Garcia JG (2007) A variant of the myosin light chain kinase gene is associated with severe asthma in African Americans. Genet Epidemiol 31(4):296–305

    Article  PubMed  Google Scholar 

  • Frank PG, Woodman SE, Park DS, Lisanti MP (2003) Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23(7):1161–1168

    Article  CAS  PubMed  Google Scholar 

  • Gao X, Kouklis P, Xu N, Minshall RD, Sandoval R, Vogel SM, Malik AB (2000) Reversibility of increased microvessel permeability in response to VE-cadherin disassembly. Am J Physiol Lung Cell Mol Physiol 279(6):L1218–L1225

    CAS  PubMed  Google Scholar 

  • Gao L, Grant A, Halder I, Brower R, Sevransky J, Maloney JP, Moss M, Shanholtz C, Yates CR, Meduri GU, Shriver MD, Ingersoll R, Scott AF, Beaty TH, Moitra J, Ma SF, Ye SQ, Barnes KC, Garcia JG (2006) Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol 34(4):487–495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao L, Grant AV, Rafaels N, Stockton-Porter M, Watkins T, Gao P, Chi P, Munoz M, Watson H, Dunston G, Togias A, Hansel N, Sevransky J, Maloney JP, Moss M, Shanholtz C, Brower R, Garcia JG, Grigoryev DN, Cheadle C, Beaty TH, Mathias RA, Barnes KC (2007) Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma. J Allergy Clin Immunol 119:1111–1118, United States

    Article  CAS  PubMed  Google Scholar 

  • Garcia JG, Schaphorst KL (1995) Regulation of endothelial cell gap formation and paracellular permeability. J Investig Med 43(2):117–126

    CAS  PubMed  Google Scholar 

  • Garcia JG, Davis HW, Patterson CE (1995) Regulation of endothelial cell gap formation and barrier dysfunction: role of myosin light chain phosphorylation. J Cell Physiol 163(3):510–522

    Article  CAS  PubMed  Google Scholar 

  • Garcia JG, Verin AD, Schaphorst K, Siddiqui R, Patterson CE, Csortos C, Natarajan V (1999) Regulation of endothelial cell myosin light chain kinase by Rho, cortactin, and p60(src). Am J Physiol 276(6 Pt 1):L989–L998

    CAS  PubMed  Google Scholar 

  • Geiger B, Bershadsky A, Pankov R, Yamada KM (2001) Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2(11):793–805

    Article  CAS  PubMed  Google Scholar 

  • Gil J (2011) Microcirculation of the lung: functional and anatomic aspects. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 13–24

    Chapter  Google Scholar 

  • Goeckeler ZM, Wysolmerski RB (1995) Myosin light chain kinase-regulated endothelial cell contraction: the relationship between isometric tension, actin polymerization, and myosin phosphorylation. J Cell Biol 130(3):613–627

    Article  CAS  PubMed  Google Scholar 

  • Gong MC, Iizuka K, Nixon G, Browne JP, Hall A, Eccleston JF, Sugai M, Kobayashi S, Somlyo AV, Somlyo AP (1996) Role of guanine nucleotide-binding proteins ras-family or trimeric proteins or both in Ca2+ sensitization of smooth muscle. Proc Natl Acad Sci U S A 93(3):1340–1345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo M, Breslin JW, Wu MH, Gottardi CJ, Yuan SY (2008) VE-cadherin and beta-catenin binding dynamics during histamine-induced endothelial hyperpermeability. Am J Physiol Cell Physiol 294(4):C977–C984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasunuma K, Rodman DM, McMurtry IF (1991) Effects of K+ channel blockers on vascular tone in the perfused rat lung. Am Rev Respir Dis 144(4):884–887

    Article  CAS  PubMed  Google Scholar 

  • Hirase T, Kawashima S, Wong EY, Ueyama T, Rikitake Y, Tsukita S, Yokoyama M, Staddon JM (2001) Regulation of tight junction permeability and occludin phosphorylation by Rhoa-p160ROCK-dependent and -independent mechanisms. J Biol Chem 276(13):10423–10431

    Article  CAS  PubMed  Google Scholar 

  • Huang ZF, Wun TC, Broze GJ (1993) Kinetics of factor Xa inhibition by tissue factor pathway inhibitor. J Biol Chem 268(36):26950–26955

    CAS  PubMed  Google Scholar 

  • Jesty J, Wun TC, Lorenz A (1994) Kinetics of the inhibition of factor Xa and the tissue factor-factor VIIa complex by the tissue factor pathway inhibitor in the presence and absence of heparin. Biochemistry 33(42):12686–12694

    Article  CAS  PubMed  Google Scholar 

  • Komarova Y, Malik AB (2010) Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol 72:463–493

    Article  CAS  PubMed  Google Scholar 

  • Landis EM, Hortenstine JC (1950) Functional significance of venous blood pressure. Physiol Rev 30:1–32

    CAS  PubMed  Google Scholar 

  • Li S, Seitz R, Lisanti MP (1996) Phosphorylation of caveolin by src tyrosine kinases. The alpha-isoform of caveolin is selectively phosphorylated by v-Src in vivo. J Biol Chem 271(7):3863–3868

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Sham JS, Shimoda LA, Kuppusamy P, Sylvester JT (2003) Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 285(2):L322–L333

    Article  CAS  PubMed  Google Scholar 

  • Machleidt T, Li WP, Liu P, Anderson RG (2000) Multiple domains in caveolin-1 control its intracellular traffic. J Cell Biol 148(1):17–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackman N, Sawdey MS, Keeton MR, Loskutoff DJ (1993) Murine tissue factor gene expression in vivo. Tissue and cell specificity and regulation by lipopolysaccharide. Am J Pathol 143(1):76–84

    CAS  PubMed  PubMed Central  Google Scholar 

  • Majno G, Palade GE (1961) Studies on inflammation. I. the effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol 11:607–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majno G, Palade GE, Schoefl GI (1961) Studies on inflammation. II. the site of action of histamine and serotonin along the vascular tree: a topographic study. J Biophys Biochem Cytol 11:607–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandegar M, Fung YC, Huang W, Remillard CV, Rubin LJ, Yuan JX (2004) Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res 68(2):75–103

    Article  CAS  PubMed  Google Scholar 

  • Mantovani A, Bussolino F, Introna M (1997) Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today 18(5):231–240

    Article  CAS  PubMed  Google Scholar 

  • Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T (1992) Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett 307(3):287–293

    Article  CAS  PubMed  Google Scholar 

  • Matthay MA, Ware LB, Zimmerman GA (2012) The acute respiratory distress syndrome. J Clin Invest 122(8):2731–2740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMurtry IF (1985) BAY K 8644 potentiates and A23187 inhibits hypoxic vasoconstriction in rat lungs. Am J Physiol 249(4 Pt 2):H741–H746

    CAS  PubMed  Google Scholar 

  • McMurtry IF, Davidson AB, Reeves JT, Grover RF (1976) Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res 38(2):99–104

    Article  CAS  PubMed  Google Scholar 

  • Mehta D, Malik AB (2006) Signaling mechanisms regulating endothelial permeability. Physiol Rev 86(1):279–367

    Article  CAS  PubMed  Google Scholar 

  • Mellion BT, Ignarro LJ, Ohlstein EH, Pontecorvo EG, Hyman AL, Kadowitz PJ (1981) Evidence for the inhibitory role of guanosine 3′, 5′-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 57(5):946–955

    CAS  PubMed  Google Scholar 

  • Michel CC, Curry FE (1999) Microvascular permeability. Physiol Rev 79(3):703–761

    CAS  PubMed  Google Scholar 

  • Michelakis ED, Hampl V, Nsair A, Wu X, Harry G, Haromy A, Gurtu R, Archer SL (2002a) Diversity in mitochondrial function explains differences in vascular oxygen sensing. Circ Res 90(12):1307–1315

    Article  CAS  PubMed  Google Scholar 

  • Michelakis ED, McMurtry MS, Wu XC, Dyck JR, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R, Archer SL (2002b) Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels. Circulation 105(2):244–250

    Article  CAS  PubMed  Google Scholar 

  • Minshall RD, Malik AB (2006) Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol 176(Pt 1):107–144

    Article  Google Scholar 

  • Minshall RD, Tiruppathi C, Vogel SM, Niles WD, Gilchrist A, Hamm HE, Malik AB (2000) Endothelial cell-surface gp60 activates vesicle formation and trafficking via G(i)-coupled Src kinase signaling pathway. J Cell Biol 150(5):1057–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirzapoiazova T, Moitra J, Moreno-Vinasco L, Sammani S, Turner JR, Chiang ET, Evenoski C, Wang T, Singleton PA, Huang Y, Lussier YA, Watterson DM, Dudek SM, Garcia JG (2011) Non-muscle myosin light chain kinase isoform is a viable molecular target in acute inflammatory lung injury. Am J Respir Cell Mol Biol 44:40–52, United States

    Article  CAS  PubMed  Google Scholar 

  • Moore KL, Andreoli SP, Esmon NL, Esmon CT, Bang NU (1987) Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 79(1):124–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan JP, Morgan KG (1984) Stimulus-specific patterns of intracellular calcium levels in smooth muscle of ferret portal vein. J Physiol 351:155–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moudgil R, Michelakis ED, Archer SL (2005) Hypoxic pulmonary vasoconstriction. J Appl Physiol (1985) 98(1):390–403

    Article  CAS  Google Scholar 

  • Moudgil R, Michelakis ED, Archer SL (2006) The role of K+ channels in determining pulmonary vascular tone, oxygen sensing, cell proliferation, and apoptosis: implications in hypoxic pulmonary vasoconstriction and pulmonary arterial hypertension. Microcirculation 13(8):615–632

    Article  CAS  PubMed  Google Scholar 

  • Murray TR, Chen L, Marshall BE, Macarak EJ (1990) Hypoxic contraction of cultured pulmonary vascular smooth muscle cells. Am J Respir Cell Mol Biol 3(5):457–465

    Article  CAS  PubMed  Google Scholar 

  • Nelson MT, Quayle JM (1995) Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268(4 Pt 1):C799–C822

    CAS  PubMed  Google Scholar 

  • Ozawa M, Kemler R (1998) Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. J Biol Chem 273(11):6166–6170

    Article  CAS  PubMed  Google Scholar 

  • Paky A, Michael JR, Burke-Wolin TM, Wolin MS, Gurtner GH (1993) Endogenous production of superoxide by rabbit lungs: effects of hypoxia or metabolic inhibitors. J Appl Physiol (1985) 74(6):2868–2874

    CAS  Google Scholar 

  • Pappenheimer JR, Renkin EM, Borrero LM (1951) Filtration, diffusion and molecular sieving through capillary membranes: a contribution to pore theory of capillary permeability. Am J Physiol 167:13–46

    CAS  PubMed  Google Scholar 

  • Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7(10):803–815

    Article  CAS  PubMed  Google Scholar 

  • Post JM, Hume JR, Archer SL, Weir EK (1992) Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 262(4 Pt 1):C882–C890

    CAS  PubMed  Google Scholar 

  • Predescu D, Palade GE (1993) Plasmalemmal vesicles represent the large pore system of continuous microvascular endothelium. Am J Physiol 265(2 Pt 2):H725–H733

    CAS  PubMed  Google Scholar 

  • Qiao RL, Yan W, Lum H, Malik AB (1995) Arg-Gly-Asp peptide increases endothelial hydraulic conductivity: comparison with thrombin response. Am J Physiol 269(1 Pt 1):C110–C117

    CAS  PubMed  Google Scholar 

  • Quinsey NS, Greedy AL, Bottomley SP, Whisstock JC, Pike RN (2004) Antithrombin: in control of coagulation. Int J Biochem Cell Biol 36(3):386–389

    Article  CAS  PubMed  Google Scholar 

  • Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276(41):38121–38138

    CAS  PubMed  Google Scholar 

  • Reeve HL, Weir EK, Nelson DP, Peterson DA, Archer SL (1995) Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue. Exp Physiol 80(5):825–834

    Article  CAS  PubMed  Google Scholar 

  • Renkin EM, Carter RD, Joyner WL (1974) Mechanism of the sustained action of histamine and bradykinin on transport of large molecules across capillary walls in the dog paw. Microvasc Res 7(1):49–60

    Article  CAS  PubMed  Google Scholar 

  • Rounds S, McMurtry IF (1981) Inhibitors of oxidative ATP production cause transient vasoconstriction and block subsequent pressor responses in rat lungs. Circ Res 48(3):393–400

    Article  CAS  PubMed  Google Scholar 

  • Sargiacomo M, Scherer PE, Tang Z, Kübler E, Song KS, Sanders MC, Lisanti MP (1995) Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc Natl Acad Sci U S A 92(20):9407–9411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, Chardin P, Pacaud P, Loirand G (2000) Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275(28):21722–21729

    Article  CAS  PubMed  Google Scholar 

  • Schlegel A, Lisanti MP (2000) A molecular dissection of caveolin-1 membrane attachment and oligomerization. Two separate regions of the caveolin-1 C-terminal domain mediate membrane binding and oligomer/oligomer interactions in vivo. J Biol Chem 275(28):21605–21617

    Article  CAS  PubMed  Google Scholar 

  • Schouten M, Wiersinga WJ, Levi M, van der Poll T (2008) Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol 83(3):536–545

    Article  CAS  PubMed  Google Scholar 

  • Schubert W, Frank PG, Woodman SE, Hyogo H, Cohen DE, Chow CW, Lisanti MP (2002) Microvascular hyperpermeability in caveolin-1(−/−) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 277(42):40091–40098

    Article  CAS  PubMed  Google Scholar 

  • Seeley EJ, Matthay MA, Wolters PJ (2012) Inflection points in sepsis biology: from local defense to systemic organ injury. Am J Physiol Lung Cell Mol Physiol 303(5):L355–L363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shasby DM, Ries DR, Shasby SS, Winter MC (2002) Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin. Am J Physiol Lung Cell Mol Physiol 282(6):L1330–L1338

    Article  CAS  PubMed  Google Scholar 

  • Shimoda LA, Manalo DJ, Sham JS, Semenza GL, Sylvester JT (2001) Partial HIF-1 alpha deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 281(1):L202–L208

    CAS  PubMed  Google Scholar 

  • Siflinger-Birnboim A, Del Vecchio PJ, Cooper JA, Blumenstock FA, Shepard JM, Malik AB (1987) Molecular sieving characteristics of the cultured endothelial monolayer. J Cell Physiol 132(1):111–117

    Article  CAS  PubMed  Google Scholar 

  • Siflinger-Birnboim A, Cooper JA, del Vecchio PJ, Lum H, Malik AB (1988) Selectivity of the endothelial monolayer: effects of increased permeability. Microvasc Res 36(3):216–227

    Article  CAS  PubMed  Google Scholar 

  • Somlyo AP, Somlyo AV (1994) Signal transduction and regulation in smooth muscle. Nature 372(6503):231–236

    Article  CAS  PubMed  Google Scholar 

  • Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83(4):1325–1358

    Article  CAS  PubMed  Google Scholar 

  • Strieter RM, Kunkel SL (1994) Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 42(4):640–651

    CAS  PubMed  Google Scholar 

  • Sylvester JT, Shimoda LA, Aaronson PI, Ward JP (2012) Hypoxic pulmonary vasoconstriction. Physiol Rev 92(1):367–520

    Article  CAS  PubMed  Google Scholar 

  • Tolins M, Weir EK, Chesler E, Nelson DP, From AH (1986) Pulmonary vascular tone is increased by a voltage-dependent calcium channel potentiator. J Appl Physiol (1985) 60(3):942–948

    CAS  Google Scholar 

  • van Hinsbergh VW (2012) Endothelium – role in regulation of coagulation and inflammation. Semin Immunopathol 34(1):93–106

    Article  PubMed  CAS  Google Scholar 

  • van Nieuw AG, Minshall R, Malik A (2011) Caveolae and signaling in pulmonary vascular endothelial and smooth muscle cells. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 273–285

    Google Scholar 

  • Vaporciyan AA, DeLisser HM, Yan HC, Mendiguren II, Thom SR, Jones ML, Ward PA, Albelda SM (1993) Involvement of platelet-endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo. Science 262(5139):1580–1582

    Article  CAS  PubMed  Google Scholar 

  • Visovatti S, Ohtsuka T, Pinsky DL (2011) Interactions of leukocytes and coagulation factors with the vessel wall. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 399–410

    Chapter  Google Scholar 

  • Vogel SM, Malik AB (2012) Cytoskeletal dynamics and lung fluid balance. Compr Physiol 2(1):449–478

    Article  PubMed  Google Scholar 

  • Von Euler U, Liljestrand G (1946) Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 12:301–320

    Article  Google Scholar 

  • Wang J, Zhang D, Remillard CV, Yuan JX-J (2011) Pathogenic roles of Ca2+ and ion channels in hypoxia-mediated pulmonary hypertension. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 683–694

    Chapter  Google Scholar 

  • Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342(18):1334–1349

    Article  CAS  PubMed  Google Scholar 

  • Waypa GB, Chandel NS, Schumacker PT (2001) Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res 88(12):1259–1266

    Article  CAS  PubMed  Google Scholar 

  • Weiler H, Isermann BH (2003) Thrombomodulin. J Thromb Haemost 1(7):1515–1524

    Article  CAS  PubMed  Google Scholar 

  • Weir EK, López-Barneo J, Buckler KJ, Archer SL (2005) Acute oxygen-sensing mechanisms. N Engl J Med 353(19):2042–2055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weir K, Cabera J, Peterson D, Mahapatra S, Hong Z (2011) Hypoxic pulmonary vasoconstriction. In: Yuan J, Garcia J, Hales C, Rich S, Archer S, West J (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 675–682

    Chapter  Google Scholar 

  • Weisberg HF (1978) Osmotic pressure of the serum proteins. Ann Clin Lab Sci 8(2):155–164

    CAS  PubMed  Google Scholar 

  • West JB (2013a) Fragility of pulmonary capillaries. J Appl Physiol (1985) 115(1):1–15

    Article  Google Scholar 

  • West JB (2013b) Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation. Am J Physiol Regul Integr Comp Physiol 304(3):R171–R176

    Article  CAS  PubMed  Google Scholar 

  • West JB, Dollery CT, Naimark A (1964) Distribution of blood flow in isolated lungs; relation to vascular and alveolar pressures. J Appl Physiol 19:713–724

    CAS  PubMed  Google Scholar 

  • Wojciak-Stothard B, Tsang LY, Haworth SG (2005) Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 288(4):L749–L760

    Article  CAS  PubMed  Google Scholar 

  • Wu MH, Ustinova E, Granger HJ (2001) Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules. J Physiol 532(Pt 3):785–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto K, de Waard V, Fearns C, Loskutoff DJ (1998) Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo. Blood 92(8):2791–2801

    CAS  PubMed  Google Scholar 

  • Yu AY, Shimoda LA, Iyer NV, Huso DL, Sun X, McWilliams R, Beaty T, Sham JS, Wiener CM, Sylvester JT, Semenza GL (1999) Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 alpha. J Clin Invest 103(5):691–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan JX-J, Tod ML, Rubin LJ, Blaustein MP (1990) Contrasting effects of hypoxia on tension in rat pulmonary and mesenteric arteries. Am J Physiol 259(2 Pt 2):H281–H289

    CAS  PubMed  Google Scholar 

  • Yuan XJ, Goldman WF, Tod ML, Rubin LJ, Blaustein MP (1993) Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 264(2 Pt 1):L116–L123

    CAS  PubMed  Google Scholar 

  • Yuan XJ, Tod ML, Rubin LJ, Blaustein MP (1995) Hypoxic and metabolic regulation of voltage-gated K+ channels in rat pulmonary artery smooth muscle cells. Exp Physiol 80(5):803–813

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Singleton PA, Brown ME, Dudek SM, Garcia JG (2009) Phosphotyrosine protein dynamics in cell membrane rafts of sphingosine-1-phosphate-stimulated human endothelium: role in barrier enhancement. Cell Signal 21(12):1945–1960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois College of Medicine, 909 South Wolcott Avenue COMRB 3131 (MC 719), Chicago, IL, 60612, USA

    Alicia N. Rizzo & Jason X.-J. Yuan

  2. Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Alicia N. Rizzo & Jason X.-J. Yuan

  3. Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, 909 South Wolcott Avenue COMRB 3131 (MC 719), Chicago, IL, 60612, USA

    Dustin R. Fraidenburg

Authors
  1. Alicia N. Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dustin R. Fraidenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason X.-J. Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason X.-J. Yuan .

Editor information

Editors and Affiliations

  1. Division of Cardiovascular Disease Department of Internal Medicine, Health Care Center Bitterfeld, Bitterfeld-Wolfen, Germany

    Peter Lanzer

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Rizzo, A.N., Fraidenburg, D.R., Yuan, J.XJ. (2015). Pulmonary Vascular Physiology and Pathophysiology. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37078-6_202

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-37078-6_202

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-37077-9

  • Online ISBN: 978-3-642-37078-6

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation