AJP - Heart and Circulatory Physiology, Vol 270, Issue 1 7-15, Copyright © 1996 by American Physiological Society

ARTICLES

Endotoxin pretreatment enhances portal venous contractile response to endothelin-1

B. H. Pannen, M. Bauer, J. X. Zhang, J. L. Robotham and M. G. Clemens
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.

To test whether endotoxin pretreatment modulates the portal hemodynamic response to endothelin (ET)-1 and phenylephrine (PE), two potent vasoconstrictors in the portal circulation of the normal liver, rats received intraperitoneal injections of Escherichia coli lipopolysaccharide (LPS; 1 mg/kg body wt) or saline. Livers were isolated after 6 or 24 h and perfused with Krebs buffer containing 5% autologous erythrocytes. Analyses of portal pressure-flow (P-Q) relationships and epifluorescence video microscopy were performed before and after ET-1 (10(-9) M) or PE (10(-5) M) administration. LPS pretreatment increased total portal resistances (Rt), zero-flow pressures (PQ = 0), and linear regression slopes of P-Q relationships, and decreased the sinusoidal diameters (Ds) and sinusoidal volumetric flow (Qv). The response to ET-1 was enhanced 6 and 24 h after LPS administration, leading to greater increases in Rt, PQ = 0, and slope and more pronounced decreases in Dx, red blood cell velocity (VRBC), and Qv. In contrast, PE effects were similar (PQ = 0, slope, Ds) or even attenuated (Rt, VRBC, Qv) in livers from LPS-treated compared with control animals. Thus endotoxin pretreatment increased the portal contractile response to ET-1 but not to PE. This enhanced ET-1 response appeared to occur at sinusoidal and presinusoidal levels and may contribute to endotoxin-induced hepatic microcirculatory failure.

This article has been cited by other articles:

				H. Xu, K. Korneszczuk, A. Karaa, T. Lin, M. G. Clemens, and J. X. Zhang Thromboxane A2 from Kupffer cells contributes to the hyperresponsiveness of hepatic portal circulation to endothelin-1 in endotoxemic rats Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G277 - G283. [Abstract] [Full Text] [PDF]

				Y. Yokoyama, B. Toth, W. C. Kitchens, M. G. Schwacha, K. I. Bland, and I. H. Chaudry Role of thromboxane in producing portal hypertension following trauma-hemorrhage Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1293 - G1299. [Abstract] [Full Text] [PDF]

				B. H. J. Pannen New Insights Into the Regulation of Hepatic Blood Flow After Ischemia and Reperfusion Anesth. Analg., June 1, 2002; 94(6): 1448 - 1457. [Full Text] [PDF]

				B. H. J. Pannen, S. Schroll, T. Loop, M. Bauer, A. Hoetzel, and K. K. Geiger Hemorrhagic shock primes the hepatic portal circulation for the vasoconstrictive effects of endothelin-1 Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1075 - H1084. [Abstract] [Full Text] [PDF]

				Y. Yokoyama, R. Baveja, N. Sonin, M. G. Clemens, and J. X. Zhang Hepatic neovascularization after partial portal vein ligation: novel mechanism of chronic regulation of blood flow Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G21 - G31. [Abstract] [Full Text] [PDF]

				A. T. Eakes and M. S. Olson Regulation of endothelin synthesis in hepatic endothelial cells Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G1068 - G1076. [Abstract] [Full Text] [PDF]