K. Sakai et al., SYNERGISTIC EFFECT OF CALCITONIN-GENE-RELATED PEPTIDE ON ADENOSINE-INDUCED VASODEPRESSION IN RATS, European journal of pharmacology, 344(2-3), 1998, pp. 153-159
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.