Synergistic effect of calcitonin gene-related peptide on adenosine-induced vasodepression in rats

The action of calcitonin gene-related peptide (CGRP) on the vasodepressor response to adenosine was investigated in anesthetized rats. I.v. bolus injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg), isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10-300 microg/kg) produced dose-dependent decreases in blood pressure, accompanied by changes in heart rate. Only the vasodepressor response elicited by adenosine, among the agents tested, was significantly enhanced by i.v. infusion of either CGRP (1 ng/kg per min) or cromakalim (0.1 microg/kg per min), which possesses glibenclamide-sensitive K+ channel opening activity. After i.v. treatment with glibenclamide (20 mg/kg), the vasodepressor responses not only to adenosine but also to CGRP (0.5 microg/kg) and cromakalim (30 microg/kg) were significantly 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, seems to be mediated at least partly through ATP-sensitive K+ channel activation.