In vitro and in vivo vascular responses to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis

A substance which increases the entry of extracellular calcium into arteria l smooth muscle may decrease cirrhosis-induced vasodilation. The aim of the present study was to measure the effects of the L-type Ca2+ channel activa tor, Bay K 8644, on the haemodynamics of rats with cirrhosis. Vascular reac tivity to this substance was also investigated. Splanchnic and systemic hae modynamic responses to Bay K 8644 (50 mu g/kg) were measured in cirrhotic a nd normal rats. Contraction induced by 0.1 mu mol/L Bay K 8644 was measured in arterial rings (aorta and superior mesenteric artery) from cirrhotic an d normal rats. In cirrhotic rats, Bay K 8644 significantly decreased portal pressure (15%) and portal tributary blood flow (24%), significantly increa sed portal territory vascular resistance (54%) and did not significantly ch ange hepatocollateral vascular resistance. Bay K 8644 significantly increas ed arterial pressure (7%) and systemic vascular resistance (24%) and did no t change the cardiac index. In normal rats, Bay K 8644 significantly increa sed vascular resistance (150%) in portal, hepatocollateral and systemic ter ritories and significantly decreased the cardiac index (44%). Changes in po rtal territory, hepatocollateral and systemic vascular resistances were sig nificantly less marked in cirrhotic than in normal rats. In rings from the aorta and superior mesenteric artery, Bay K 8644-induced contraction was si gnificantly lower in cirrhotic than in normal rats. In conclusion, in rats with cirrhosis, Bay K 8644 administration reduced vasodilation in splanchni c and systemic arteries and did not affect hepatocollateral vascular resist ance. The Bay K 8644-induced reduction in splanchnic vasodilation caused a decrease in portal hypertension. This study also shows that Bay K 8644-indu ced vascular contraction was less marked in cirrhotic than in normal rats, in systemic and splanchnic vascular beds.