Skip to main content
SpringerLink
Log in

Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Hydrogen sulfide (H2S) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of H2S production within the gut lumen; this source of H2S is primarily produced and detoxified in the colon under physiologic conditions. Nitric oxide (NO), a major endogenous vasodilator in the portal circulation, participates in H2S-induced vasodilation in some vascular beds. We hypothesize that jejunal but not colonic H2S increases portal vein flow in a NO-dependent fashion. To evaluate the effects of luminal H2S, venous blood flow, portal venous pressure, and systemic venous pressure were measured in rats after administration of either vehicle or an H2S donor (NaHS) into the jejunum or the colon. We found that portal venous pressure and systemic pressure did not change and were similar between the three study groups. However, portal venous blood flow significantly increased following jejunal administration of NaHS but not in response to colonic NaHS or vehicle administration. To test the contribution of NO production to this response, another group of animals was treated with either an NO synthase inhibitor (N-Ω-nitro-l-arginine, L-NNA) or saline prior to jejunal NaHS infusion. After L-NNA pretreatment, NaHS caused a significant fall rather than increase in portal venous flow compared to saline pretreatment. These data demonstrate that H2S within the small intestine significantly increases portal venous blood flow in a NO-dependent fashion.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kanagy NL, Szabo C, Papapetropoulos A. Vascular biology of hydrogen sulfide. Am J Physiol Cell Physiol. 2017;312:C537–C549.

    Article  Google Scholar 

  2. Naik JS, Osmond JM, Walker BR, Kanagy NL. Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels. Am J Physiol Hear Circ Physiol. 2016;311:H1437–H1444.

    Article  Google Scholar 

  3. Mani S, Cao W, Wu L, Wang R. Hydrogen sulfide and the liver. Nitric Oxide Biol Chem. 2014;41:62–71.

    Article  CAS  Google Scholar 

  4. Norris EJ, Feilen N, Nguyen NH, et al. Hydrogen sulfide modulates sinusoidal constriction and contributes to hepatic micorcirculatory dysfunction during endotoxemia. Am J Physiol Gastrointest Liver Physiol. 2013;304:G1070–G1078.

    Article  CAS  Google Scholar 

  5. Fiorucci S, Antonelli E, Mencarelli A, et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology. 2005;42:539–548.

    Article  CAS  Google Scholar 

  6. Feng X, Zhang H, Shi M, Chen Y, Yang T, Fan H. Toxic effects of hydrogen sulfide donor NaHS induced liver apoptosis is regulated by complex IV subunits and reactive oxygen species generation in rats. Environ Toxicol. 2020;35:322–332.

    Article  CAS  Google Scholar 

  7. Wallace JL, Ferraz JGP, Muscara MN. Hydrogen sulfide: an endogenous mediator of resolution of inflammation and injury. Antioxidants Redox Signal. 2012;17:58–67.

    Article  CAS  Google Scholar 

  8. Nakamura N, Lin HC, McSweeney CS, Mackie RI, Gaskins HR. Mechanisms of microbial hydrogen disposal in the human colon and implications for health and disease. Annu Rev Food Sci Technol. 2010;1:363–395.

    Article  CAS  Google Scholar 

  9. Barton LL, Ritz NL, Fauque GD, Lin HC. Sulfur cycling and the intestinal microbiome. Dig Dis Sci. 2017;62:2241–2257. https://doi.org/10.1007/s10620-017-4689-5.

    Article  CAS  PubMed  Google Scholar 

  10. Levitt MD, Furne J, Springfield J, Suarez F, DeMaster E. Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa. J Clin Investig. 1999;104:1107–1114.

    Article  CAS  Google Scholar 

  11. Beaumont M, Andriamihaja M, Lan A, et al. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: the adaptive response. Free Radic Biol Med. 2016;93:155–164.

    Article  CAS  Google Scholar 

  12. Furne J, Springfield J, Koenig T, DeMaster E, Levitt MD. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa. Biochem Pharmacol. 2001;62:255–259.

    Article  CAS  Google Scholar 

  13. Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis: current status and future directions. J Hepatol. 2014;61:912–924.

    Article  CAS  Google Scholar 

  14. Gaynullina DK, Sofronova SI, Selivanova EK, et al. NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism. Nitric Oxide Biol Chem. 2017;63:21–28.

    Article  CAS  Google Scholar 

  15. Suarez F, Furne J, Springfield J, Levitt M. Production and elimination of sulfur-containing gases in the rat colon. Am J Physiol. 1998;274:727–733.

    Google Scholar 

  16. Lin HC. Small intestinal bacterial overgrowth. JAMA. 2004;292:852.

    Article  CAS  Google Scholar 

  17. Hee Kang S, Young Kim M, Koo Baik S. SPECIAL ISSUE-PORTAL HYPERTENSION Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon. Hepatol Int. 2012;12:112–121.

    Article  Google Scholar 

  18. Tumgor G. Cirrhosis and hepatopulmonary syndrome. World J Gastroenterol. 2014;20:2586–2594.

    Article  Google Scholar 

  19. Arroyo V, Ginés P. Arteriolar vasodilation and the pathogenesis of the hyperdynamic circulation and renal sodium and water retention in cirrhosis. Gastroenterology. 1992;102:1077–1079.

    Article  CAS  Google Scholar 

  20. Møller S, Bendtsen F. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis. Liver Int. 2018;38:570–580.

    Article  Google Scholar 

  21. Bolognesi M, Di Pascoli M, Verardo A, Gatta A. Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis. World J Gastroenterol. 2014;20:2555–2563.

    Article  Google Scholar 

  22. Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Dig Dis. 2016;34:382–386.

    Article  Google Scholar 

  23. Huc T, Jurkowska H, Wróbel M, Jaworska K, Onyszkiewicz M, Ufnal M. Colonic hydrogen sulfide produces portal hypertension and systemic hypotension in rats. Exp Biol Med. 2018;243:96–106.

    Article  CAS  Google Scholar 

  24. Matallo J, Vogt J, Mccook O, et al. Sulfide-inhibition of mitochondrial respiration at very low oxygen concentrations. Nitric Oxide Biol Chem. 2014;41:79–84.

    Article  CAS  Google Scholar 

  25. Hildebrandt MA, Hoffman C, Sherrill-Mix SA, et al. High fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009. https://doi.org/10.1053/j.gastro.2009.08.042.

    Article  PubMed  Google Scholar 

  26. Blaser MJ. Antibiotic use and its consequences for the normal microbiome. Science. 2016;352:544–545.

    Article  CAS  Google Scholar 

  27. Mackos AR, Maltz R, Bailey MT. The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation. Horm Behav. 2017;88:70–78.

    Article  CAS  Google Scholar 

  28. Chassard C, Dapoigny M, Scott KP, et al. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther. 2012;35:828–838.

    Article  CAS  Google Scholar 

  29. Norris EJ, Culberson CR, Narasimhan S, Clemens MG. The liver as a central regulator of hydrogen sulfide. Shock. 2011;36:242–250.

    Article  CAS  Google Scholar 

  30. Henao-Mejia J, Elinav E, Thaiss CA, Licona-Limon P, Flavell RA. Role of the intestinal microbiome in liver disease. J Autoimmun. 2013;46:66–73.

    Article  CAS  Google Scholar 

  31. Da Silva HE, Teterina A, Comelli EM, et al. Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Sci Rep. 2018. https://doi.org/10.1038/s41598-018-19753-9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Xie G, Wang X, Liu P, Wei R, Chen W, Rajani C, et al. Distinctly altered gut microbiota in the progression of liver disease. 2016; [cited 2020 May 4]. www.impactjournals.com/oncotarget.

  33. Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005;41:422–433.

    Article  CAS  Google Scholar 

  34. Runyon BA, Squier S, Borzio M. Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol. 1994;21:792–796.

    Article  CAS  Google Scholar 

  35. Guarner C, González-Navajas JM, Sánchez E, et al. The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation. Hepatology. 2006;44:633–639.

    Article  CAS  Google Scholar 

  36. García-Pagán JC, Gracia-Sancho J, Bosch J. Functional aspects on the pathophysiology of portal hypertension in cirrhosis. J Hepatol. 2012;57:458–461.

    Article  Google Scholar 

  37. Iwakiri Y. Pathophysiology of portal hypertension. Clin Liver Dis. 2014;18:281–291.

    Article  Google Scholar 

  38. Acharya C, Bajaj JS. Accepted manuscript the microbiome in cirrhosis and its complications. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.08.008.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Albillos A, Bañares R, González M, et al. The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis. Gut. 2007;56:259–264.

    Article  CAS  Google Scholar 

  40. Ginés P, Quintero E, Arroyo V, et al. Compensated cirrhosis: Natural history and prognostic factors. Hepatology. 1987;7:122–128.

    Article  Google Scholar 

Download references

Acknowledgments

This study is supported, in part, by: University of New Mexico Research Allocation Grant and HL123301. Dr. Lin was supported, in part, by the Winkler Bacterial Overgrowth Research Fund.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, MSC10-5550, 1 University of New Mexico, Albuquerque, NM, 87131, USA

    Aleksandr Birg & Henry C. Lin

  2. New Mexico VA Health Care System, Albuquerque, NM, 87108, USA

    Henry C. Lin

  3. Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, 87131, USA

    Nancy Kanagy

Authors
  1. Aleksandr Birg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry C. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nancy Kanagy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aleksandr Birg.

Ethics declarations

Conflict of interest

The authors have related IP rights.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Birg, A., Lin, H.C. & Kanagy, N. Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats. Dig Dis Sci 66, 2661–2668 (2021). https://doi.org/10.1007/s10620-020-06597-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06597-5

Keywords

Search

Navigation