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

Abstract

A substance which increases the entry of extracellular calcium into arterial smooth muscle may decrease cirrhosis-induced vasodilation. The aim of the present study was to measure the effects of the L-type Ca2+ channel activator, Bay K 8644, on the haemodynamics of rats with cirrhosis. Vascular reactivity to this substance was also investigated. Splanchnic and systemic haemodynamic responses to Bay K 8644 (50 microg/kg) were measured in cirrhotic and normal rats. Contraction induced by 0.1 micromol/L Bay K 8644 was measured in arterial rings (aorta and superior mesenteric artery) from cirrhotic and normal rats. In cirrhotic rats, Bay K 8644 significantly decreased portal pressure (15%) and portal tributary blood flow (24%), significantly increased portal territory vascular resistance (54%) and did not significantly change hepatocollateral vascular resistance. Bay K 8644 significantly increased arterial pressure (7%) and systemic vascular resistance (24%) and did not change the cardiac index. In normal rats, Bay K 8644 significantly increased vascular resistance (150%) in portal, hepatocollateral and systemic territories and significantly decreased the cardiac index (44%). Changes in portal territory, hepatocollateral and systemic vascular resistances were significantly less marked in cirrhotic than in normal rats. In rings from the aorta and superior mesenteric artery, Bay K 8644-induced contraction was significantly lower in cirrhotic than in normal rats. In conclusion, in rats with cirrhosis, Bay K 8644 administration reduced vasodilation in splanchnic and systemic arteries and did not affect hepatocollateral vascular resistance. The Bay K 8644-induced reduction in splanchnic vasodilation caused a decrease in portal hypertension. This study also shows that Bay K 8644-induced vascular contraction was less marked in cirrhotic than in normal rats, in systemic and splanchnic vascular beds.

• Authors: R Moreau, F Oberti, P Lahaye, A Gadano, S Cailmail, P Sogni, P Cales, D Lebrec
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 13 Issue 12 Pg. 1254-8 (Dec 1998) ISSN: 0815-9319 [Print] Australia
• PMID: 9918435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Agonists
• Calcium Channels
• Calcium Channels, L-Type
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Calcium

Topics

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (pharmacology)
• Animals
• Aorta (drug effects, metabolism, physiopathology)
• Calcium (metabolism)
• Calcium Channel Agonists (pharmacology)
• Calcium Channels (drug effects, metabolism)
• Calcium Channels, L-Type
• Hemodynamics (drug effects)
• In Vitro Techniques
• Liver Cirrhosis, Experimental (metabolism, physiopathology)
• Male
• Mesenteric Artery, Superior (drug effects, metabolism, physiopathology)
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects, metabolism, physiopathology)
• Portal Pressure (drug effects)
• Rats
• Rats, Sprague-Dawley