An Endothelin A Receptor Antagonist Induces Dilatation of Sinusoidal Endothelial Fenestrae: Implications for Endothelin-1 in Hepatic Microcirculation

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2007 Sep 19

PMID 17876548

Citations 9

Authors

Norihito Watanabe

Shinji Takashimizu

Yasuhiro Nishizaki

Seiichiro Kojima

Tatehiro Kagawa

Shohei Matsuzaki

Affiliations

Soon will be listed here.

Abstract

Background: Sinusoidal endothelial fenestrae (SEF) regulate the sinusoidal circulation by altering their diameter and number. This study documented the effects of endothelin (ET) receptor antagonists on SEF and hepatic microcirculation.

Methods: The portal pressure and hepatic tissue blood flow were measured with a hydromanometer and a laser Doppler blood flow meter, respectively. BQ-123 (ET(A) receptor antagonist) or BQ-788 (ET(B) receptor antagonist) was continuously infused into normal rats at the rate of 10 nmol/min for 10 min. The sinusoids were observed at 60 min after the infusion by scanning electron microscopy. The localization of ET-1 and ET(A) and ET(B) receptors was examined by the indirect immunoperoxidase method.

Results: When BQ-123 was infused, the portal pressure gradually decreased with time, and it showed a significant reduction compared with the control groups. On the other hand, a decrease in portal pressure was not evident in the BQ-788-infused groups. Hepatic tissue blood flow was maintained at the value prior to the infusion in both groups. BQ-123 also caused a marked dilatation of the SEF. The diameters of the SEF after BQ-123 infusion were almost three times those of normal SEF. ET-1 was evenly present along the sinusoidal walls, and the reaction products of the ET(A) receptors were recognized along the portal vein and in the sinusoidal cells, that is, the hepatic stellate cells and endothelial cells.

Conclusions: Action of ET-1 via the ET(A) receptors may regulate the size of SEF in addition to hepatic microcirculation.

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References

Ito Y, Abril E, Bethea N, McCuskey M, Cover C, Jaeschke H . Mechanisms and pathophysiological implications of sinusoidal endothelial cell gap formation following treatment with galactosamine/endotoxin in mice. Am J Physiol Gastrointest Liver Physiol. 2006; 291(2):G211-8. DOI: 10.1152/ajpgi.00312.2005. View

Moore K, Wendon J, Frazer M, Karani J, Williams R, Badr K . Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome. N Engl J Med. 1992; 327(25):1774-8. DOI: 10.1056/NEJM199212173272502. View

Rockey D, Chung J . Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. J Clin Invest. 1995; 95(3):1199-206. PMC: 441458. DOI: 10.1172/JCI117769. View

Stephenson K, Harvey S, Mustafa S, Eakes A, Olson M . Endothelin association with the cultured rat Kupffer cell: characterization and regulation. Hepatology. 1995; 22(3):896-905. View

Yokomori H, Oda M, Ogi M, Kamegaya Y, Tsukada N, Nakamura M . Enhanced expression of endothelin receptor subtypes in cirrhotic rat liver. Liver. 2001; 21(2):114-22. DOI: 10.1034/j.1600-0676.2001.021002114.x. View

Gupta T, Toruner M, Chung M, Groszmann R . Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology. 1998; 28(4):926-31. DOI: 10.1002/hep.510280405. View

Zhang J, Pegoli Jr W, Clemens M . Endothelin-1 induces direct constriction of hepatic sinusoids. Am J Physiol. 1994; 266(4 Pt 1):G624-32. DOI: 10.1152/ajpgi.1994.266.4.G624. View

Fukuroda T, Ozaki S, Ihara M, Ishikawa K, Yano M, Miyauchi T . Necessity of dual blockade of endothelin ETA and ETB receptor subtypes for antagonism of endothelin-1-induced contraction in human bronchi. Br J Pharmacol. 1996; 117(6):995-9. PMC: 1909802. DOI: 10.1111/j.1476-5381.1996.tb16688.x. View

Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y . A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988; 332(6163):411-5. DOI: 10.1038/332411a0. View

10.

Sakurai T, Yanagisawa M, Masaki T . Molecular characterization of endothelin receptors. Trends Pharmacol Sci. 1992; 13(3):103-8. DOI: 10.1016/0165-6147(92)90038-8. View

11.

Yokomori H, Yoshimura K, Ohshima S, Nagai T, Fujimaki K, Nomura M . The endothelin-1 receptor-mediated pathway is not involved in the endothelin-1-induced defenestration of liver sinusoidal endothelial cells. Liver Int. 2006; 26(10):1268-76. DOI: 10.1111/j.1478-3231.2006.01365.x. View

12.

Hamaoki M, Kato H, Sugi M, Fujimoto M, Kurihara H, Yosizumi M . Monoclonal antibodies to endothelin: application for sandwich immunoassays. Hybridoma. 1990; 9(1):63-9. DOI: 10.1089/hyb.1990.9.63. View

13.

Braet F, Wisse E . Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp Hepatol. 2002; 1(1):1. PMC: 131011. DOI: 10.1186/1476-5926-1-1. View

14.

HIRAKI H, Hoshi N, Hasegawa H, Tanigawa T, Emura I, Seito T . Regular immunohistochemical localization of endothelin-1 and endothelin-B receptor in normal, hyperplastic and neoplastic human adrenocortical cells. Pathol Int. 1997; 47(2-3):117-25. DOI: 10.1111/j.1440-1827.1997.tb03730.x. View

15.

Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K . Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest. 1993; 91(4):1367-73. PMC: 288108. DOI: 10.1172/JCI116338. View

16.

Braet F, de Zanger R, Baekeland M, Crabbe E, Van Der Smissen P, Wisse E . Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology. 1995; 21(1):180-9. View

17.

Takashimizu S, Watanabe N, Nishizaki Y, Kawazoe K, Matsuzaki S . Mechanisms of hepatic microcirculatory disturbances induced by acute ethanol administration in rats, with special reference to alterations of sinusoidal endothelial fenestrae. Alcohol Clin Exp Res. 1999; 23(4 Suppl):39S-46S. DOI: 10.1111/j.1530-0277.1999.tb04532.x. View

18.

GATMAITAN Z, Varticovski L, Ling L, Mikkelsen R, Steffan A, Arias I . Studies on fenestral contraction in rat liver endothelial cells in culture. Am J Pathol. 1996; 148(6):2027-41. PMC: 1861643. View

19.

Pinzani M, Failli P, Ruocco C, Casini A, Milani S, Baldi E . Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest. 1992; 90(2):642-6. PMC: 443145. DOI: 10.1172/JCI115905. View

20.

Pinzani M, Milani S, De Franco R, Grappone C, Caligiuri A, Gentilini A . Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology. 1996; 110(2):534-48. DOI: 10.1053/gast.1996.v110.pm8566602. View