SYNERGISTIC EFFECT OF CALCITONIN-GENE-RELATED PEPTIDE ON ADENOSINE-INDUCED VASODEPRESSION IN RATS

The action of calcitonin gene-related peptide (CGRP) on the vasodepres sor response to adenosine was investigated in anesthetized rats. l.v. bolus injections of adenosine (1-100 mu g/kg), acetylcholine (0.05-0.4 mu g/kg), isoproterenol (1-30 ng/kg). nitroglycerin (0.3-10 mu g/kg) and diltiazem (10-300 mu g/kg) produced dose-dependent decreases in bl ood pressure: accompanied by changes in heart rate. Only the vasodepre ssor response elicited by adenosine, among the agents tested, was sign ificantly enhanced by i.v. infusion of either CGRP (1 ng/kg per min) o r cromakalim (0.1 mu g/kg per min). which possesses glibenclamide-sens itive K+ channel opening activity. After i.v. treatment with glibencla mide (20 mg/kg), the vasodepressor responses not only to adenosine but also to CGRP (0.5 mu g/kg) and cromakalim (30 mu g/kg) were significa ntly reduced. while those to acetylcholine and isoproterenol remained unchanged. The result indicates that the enhancement of the adenosine- induced vasodepression by CGRP, like that elicited by cromakalim, seem s to be mediated at least partly through ATP-sensitive K+ channel acti vation. (C) 1998 Elsevier Science B.V.