Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Apr;91(4):1337–1342. doi: 10.1172/JCI116334

Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.

M Oshita 1, Y Takei 1, S Kawano 1, H Yoshihara 1, T Hijioka 1, H Fukui 1, M Goto 1, E Masuda 1, Y Nishimura 1, H Fusamoto 1, et al.
PMCID: PMC288104  PMID: 8473486

Abstract

This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol.

Full text

PDF
1337

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altura B. M., Altura B. T., Carella A. Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle. Br J Pharmacol. 1983 Feb;78(2):260–262. doi: 10.1111/j.1476-5381.1983.tb09389.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altura B. M., Altura B. T., Gebrewold A. Alcohol-induced spasms of cerebral blood vessels: relation to cerebrovascular accidents and sudden death. Science. 1983 Apr 15;220(4594):331–333. doi: 10.1126/science.6836278. [DOI] [PubMed] [Google Scholar]
  3. Bravo I. R., Acevedo C. G., Gallardo V. Acute effects of ethanol on liver blood circulation in the anesthetized dog. Alcohol Clin Exp Res. 1980 Jul;4(3):248–253. doi: 10.1111/j.1530-0277.1980.tb04809.x. [DOI] [PubMed] [Google Scholar]
  4. Bredfeldt J. E., Riley E. M., Groszmann R. J. Compensatory mechanisms in response to an elevated hepatic oxygen consumption in chronically ethanol-fed rats. Am J Physiol. 1985 May;248(5 Pt 1):G507–G511. doi: 10.1152/ajpgi.1985.248.5.G507. [DOI] [PubMed] [Google Scholar]
  5. Curran R. D., Billiar T. R., Stuehr D. J., Hofmann K., Simmons R. L. Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells. J Exp Med. 1989 Nov 1;170(5):1769–1774. doi: 10.1084/jem.170.5.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eguchi H., Sato N., Matsumura T., Kawano S., Kamada T. In vivo estimation of oxygen saturation of hemoglobin in hepatic lobules in rats. Adv Exp Med Biol. 1988;222:591–596. doi: 10.1007/978-1-4615-9510-6_72. [DOI] [PubMed] [Google Scholar]
  7. Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
  8. French S. W., Benson N. C., Sun P. S. Centrilobular liver necrosis induced by hypoxia in chronic ethanol-fed rats. Hepatology. 1984 Sep-Oct;4(5):912–917. doi: 10.1002/hep.1840040521. [DOI] [PubMed] [Google Scholar]
  9. Friedman S. L., Rockey D. C., McGuire R. F., Maher J. J., Boyles J. K., Yamasaki G. Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture. Hepatology. 1992 Feb;15(2):234–243. doi: 10.1002/hep.1840150211. [DOI] [PubMed] [Google Scholar]
  10. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  11. Gandhi C. R., Stephenson K., Olson M. S. Endothelin, a potent peptide agonist in the liver. J Biol Chem. 1990 Oct 15;265(29):17432–17435. [PubMed] [Google Scholar]
  12. Hayes S. N., Bove A. A. Ethanol causes epicardial coronary artery vasoconstriction in the intact dog. Circulation. 1988 Jul;78(1):165–170. doi: 10.1161/01.cir.78.1.165. [DOI] [PubMed] [Google Scholar]
  13. Hijioka T., Sato N., Matsumura T., Yoshihara H., Takei Y., Fukui H., Oshita M., Kawano S., Kamada T. Ethanol-induced disturbance of hepatic microcirculation and hepatic hypoxia. Biochem Pharmacol. 1991 Jun 1;41(11):1551–1557. doi: 10.1016/0006-2952(91)90153-v. [DOI] [PubMed] [Google Scholar]
  14. Jenkins S. A., Baxter J. N., Devitt P., Taylor I., Shields R. Effects of alcohol on hepatic haemodynamics in the rat. Digestion. 1986;34(4):236–242. doi: 10.1159/000199336. [DOI] [PubMed] [Google Scholar]
  15. Kawasaki T., Carmichael F. J., Saldivia V., Roldan L., Orrego H. Relationship between portal venous and hepatic arterial blood flows: spectrum of response. Am J Physiol. 1990 Dec;259(6 Pt 1):G1010–G1018. doi: 10.1152/ajpgi.1990.259.6.G1010. [DOI] [PubMed] [Google Scholar]
  16. Lieber C. S. Medical disorders of alcoholism. Pathogenesis and treatment. Major Probl Intern Med. 1982;22:1–589. [PubMed] [Google Scholar]
  17. Lüscher T. F. Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. Eur Heart J. 1989 Sep;10(9):847–857. doi: 10.1093/oxfordjournals.eurheartj.a059580. [DOI] [PubMed] [Google Scholar]
  18. Lüscher T. F., Yang Z., Tschudi M., von Segesser L., Stulz P., Boulanger C., Siebenmann R., Turina M., Bühler F. R. Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Circ Res. 1990 Apr;66(4):1088–1094. doi: 10.1161/01.res.66.4.1088. [DOI] [PubMed] [Google Scholar]
  19. Miyamoto K., French S. W. Hepatic adenine nucleotide metabolism measured in vivo in rats fed ethanol and a high fat-low protein diet. Hepatology. 1988 Jan-Feb;8(1):53–60. doi: 10.1002/hep.1840080111. [DOI] [PubMed] [Google Scholar]
  20. Nanji A. A., Jui L. T., French S. W. Effect of chronic carbon monoxide exposure on experimental alcoholic liver injury in rats. Life Sci. 1989;45(10):885–890. doi: 10.1016/0024-3205(89)90202-6. [DOI] [PubMed] [Google Scholar]
  21. Oshita M., Sato N., Yoshihara H., Takei Y., Hijioka T., Fukui H., Goto M., Matsunaga T., Kashiwagi T., Kawano S. Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver. Hepatology. 1992 Oct;16(4):1007–1013. doi: 10.1002/hep.1840160425. [DOI] [PubMed] [Google Scholar]
  22. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  23. Rieder H., Ramadori G., Meyer zum Büschenfelde K. H. Sinusoidal endothelial liver cells in vitro release endothelin--augmentation by transforming growth factor beta and Kupffer cell-conditioned media. Klin Wochenschr. 1991 Jun 18;69(9):387–391. doi: 10.1007/BF01647411. [DOI] [PubMed] [Google Scholar]
  24. Rubanyi G. M. Endothelium-derived relaxing and contracting factors. J Cell Biochem. 1991 May;46(1):27–36. doi: 10.1002/jcb.240460106. [DOI] [PubMed] [Google Scholar]
  25. Scholz R., Hansen W., Thurman R. G. Interaction of mixed-function oxidation with biosynthetic processes. 1. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver. Eur J Biochem. 1973 Sep 21;38(1):64–72. doi: 10.1111/j.1432-1033.1973.tb03034.x. [DOI] [PubMed] [Google Scholar]
  26. Tsuji S., Kawano S., Michida T., Masuda E., Nagano K., Takei Y., Fusamoto H., Kamada T. Ethanol stimulates immunoreactive endothelin-1 and -2 release from cultured human umbilical vein endothelial cells. Alcohol Clin Exp Res. 1992 Apr;16(2):347–349. doi: 10.1111/j.1530-0277.1992.tb01389.x. [DOI] [PubMed] [Google Scholar]
  27. Tsukamoto H., Xi X. P. Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular liver necrosis. Hepatology. 1989 Feb;9(2):302–306. doi: 10.1002/hep.1840090223. [DOI] [PubMed] [Google Scholar]
  28. Verma-Ansil B., Carmichael F. J., Saldivia V., Varghese G., Orrego H. Effect of ethanol on splanchnic hemodynamics in awake and unrestrained rats with portal hypertension. Hepatology. 1989 Dec;10(6):946–952. doi: 10.1002/hep.1840100609. [DOI] [PubMed] [Google Scholar]
  29. Withrington P. G., de Nucci G., Vane J. R. Endothelin-1 causes vasoconstriction and vasodilation in the blood perfused liver of the dog. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S209–S210. doi: 10.1097/00005344-198900135-00060. [DOI] [PubMed] [Google Scholar]
  30. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES