Effect of exogenous cholecystokinin on islet blood flow in anesthetized rats

Although a number of studies have investigated the effect of cholecystokinin (CCK) on pancreatic blood flow and exocrine function, few have addressed the effect of CCK on islet blood flow. Here, we studied the effect of exogenous CCK on islet blood flow in anesthetized rats. Islet blood flow was measured by the color microsphere method. Bolus intravenous administration of CCK (10 microg/kg) significantly increased pancreatic and islet blood flow in control Long-Evans Tokushima Otsuka (LETO) rats, but not in Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A receptors. Since fractional islet blood flow expressed as a percentage of whole pancreatic blood flow was decreased after CCK administration in LETO rats, the vasodilating effect of CCK appeared to be stronger in exocrine than endocrine tissue. Although vagotomy failed to alter the CCK-induced increase in pancreatic and islet blood flow, pretreatment with nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine completely prevented the increase in pancreatic and islet blood flow. Our results demonstrated that exogenous CCK is a potent vasodilator of exocrine as well as islet vasculature via CCK-A receptors, and that such action is mediated by a NO-dependent mechanism rather than by vagal mechanisms.