Localisation of hepatic vascular resistance sites in the isolated dual-perfused rat liver

Citation
Wx. Yang et al., Localisation of hepatic vascular resistance sites in the isolated dual-perfused rat liver, EUR J PHARM, 364(1), 1999, pp. 13-21
Citations number
33
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
00142999 → ACNP
Volume
364
Issue
1
Year of publication
1999
Pages
13 - 21
Database
ISI
SICI code
0014-2999(19990101)364:1<13:LOHVRS>2.0.ZU;2-L
Abstract
The locations of the vascular resistance sites which regulate vascular tone in the hepatic arterial and portal venous vasculatures of the rat liver we re identified using a new, in vitro, dual-perfused liver preparation. Twelv e livers of male Wistar rats were perfused via the hepatic artery and porta l vein at fixed flow and at physiological pressure. Dose-related vasoconstr iction to injections or infusions of noradrenaline was measured as transien t or sustained increases in perfusion pressure, respectively, in the hepati c arterial and portal venous vasculatures. Direct injections/infusions of n oradrenaline refer to those administered into the vasculature from which pr essure was recorded, e.g., the effects of hepatic arterial (direct) injecti ons/infusions of noradrenaline upon hepatic arterial perfusion pressure. In direct injections/infusions of noradrenaline were those administered to the adjacent afferent vasculature, e.g., the effects of portal venous (indirec t) injections of noradrenaline upon hepatic arterial perfusion pressure. Th e converse applies for recordings of portal venous perfusion pressure. The -log(M) ED50 values to direct (hepatic arterial) and indirect (portal venou s) injections in the hepatic artery were 4.25 +/- 0.20 and 3.40 +/- 0.10, r espectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (h epatic arterial) injections in the portal vein were 3.91 +/- 0.08 and 3.85 +/- 0.11, respectively, and were not significantly different (P > 0.05, Stu dent's unpaired t-test). Similarly, the -log(M) ED50 values to direct (hepa tic arterial) and indirect (portal venous) infusions in the hepatic artery were 5.28 +/- 0.11 and 3.75 +/- 0.12, respectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (hepatic arterial) infusions in the po rtal vein were 5.31 +/- 0.19 and 5.70 +/- 0.16, respectively, and were not significantly different (P > 0.05, Student's unpaired t-test). These result s demonstrated that there is little transfer of noradrenaline from the port al venous to the hepatic arterial resistance sites, but significant transfe r from the hepatic artery to the portal venous suggesting that; (a) the por tal venous resistance sites are located at the sinusoidal or post-sinusoida l level; and (b) the hepatic arterial resistance sites are located at the p re-sinusoidal level. (C) 1999 Elsevier Science B.V. All rights reserved.