Role of Ca2+-dependent potassium channels in in vitro anandamide-mediated mesenteric vasorelaxation in rats with biliary cirrhosis

Background/Aim: Anandamide can activate potassium (K+) channels to induce an endothelium-dependent vasorelaxation in normal rat mesenteric arteries. Cannabinoids contribute partly to the splanchnic vasodilation in cirrhosis. This study investigated the roles of vascular K+ channels in anandamide-induced mesenteric vasorelaxation in isolated rat cirrhotic vessels. Methods: The effects of the pretreatment of AM251, a specific CB1 receptor antagonist, were assessed on the vascular reactivity to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh) and sodium nitroprusside (SNP). Additionally, cannabinoid (CB1 and CB2) receptors' protein expression and the effects of different K+ channel blockers on vascular reactivity to anandamide were also studied. Results: Cirrhotic mesenteric arteries showed an overexpression of CB1 receptor associated with hyporeactivity to PE and KCl, and hyper-response to ACh, SNP and anandamide. Pretreatment with AM251 significantly improved the hyporeactivity to KCl and ameliorated the hyper-response to ACh in cirrhotic vessels. Increased relaxation response to anandamide was suppressed by combinations of vascular Ca2+-dependent K+ channel blockers (including apamin+charybdotoxin+iberiotoxin or apamin+TRAM-34+iberiotoxin) (TRAM-34, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole). Conclusions: In cirrhotic mesenteric arteries, vascular CB1 receptor and anandamide contribute to the in vitro hyporeactivity to KCl. In addition, hyper-response to ACh may probably act through the modulation of vascular Ca2+-dependent K+ channels.