DIFFERENTIAL-EFFECTS OF NICORANDIL ON THE VASODEPRESSOR RESPONSES TO VASOACTIVE POLYPEPTIDES ADMINISTERED INTRAVENOUSLY TO RATS

The effects of nicorandil on vasodepressor responses to vasoactive int estinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P have been examined in anaesthetized rats. Intravenous bolu s injections of VIP (0.3 mu g kg(-1)), CGRP (0.1 mu g kg(-1)) and subs tance P (0.1 mu g kg(-1)) induced reductions of blood pressure accompa nied by slight increases (less than 5%) in heart rate. Nicorandil infu sed intravenously at 10 or 30 mu g kg(-1) min(-1) significantly augmen ted the vasodepressor responses to VIP and CGRP but did not modify the responses to substance P and acetylcholine (0.1 mu g kg(-1)). Intrave nous treatment with glibenclamide (20 mu g kg(-1)) significantly atten uated not only the vasodepression caused by VIP and CGRP, but also the enhancement of the effects of the agents by nicorandil. These results indicate that nicorandil can enhance the action of VIP and CGRP, in r ats, at least partly through ATP-sensitive K+-channel activation.