Correlation of endothelium-dependent and -independent vasodilatation with liver function tests during prolonged perfusion of the rat liver.
Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100g(-1) i.p.), the livers were excised and perfused in vitro through the hepatic artery and portal vein at constant flow rates of 0.32+/-0.01 (mean+/-S.E.) and 0.98+/-0.03 ml min(-1) g liver(-1), respectively. The tone of the preparation was raised by methoxamine (7.5 x 10(-6) M). Responses to mid-range doses of acetylcholine (-11 log mol) and sodium nitroprusside (-9 log mol) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18+/-0.08) and (-log mol ED50 = 9.95+/-0.23), respectively, which did not subside until 5.5 h of perfusion. These did not coincide with the increase in activities of lactic acid dehydrogenase (LDH) and aspartate serine transaminase (AST) activity at 2.5 h, which were indicative of hepatocellular mitochondrial and cytoplasmic damage, respectively. Vascular responses suggested that there was little deterioration in endothelial or smooth muscle function in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal increases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h.
Yang
W
W
Academic Department of Surgery, Guy's King's & St Thomas' School of Medicine, St Thomas' Hospital, London, United Kingdom.
Benjamin
I S
IS
Sherwood
R
R
Alexander
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D008729:Methoxamine; D000109:Acetylcholine