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Differential effects of nicorandil on the vasodepressor responses to vasoactive polypeptides administered
1Central Research Laboratories, Chugai Pharmaceutical Co. Ltd, Tokyo, Japan.
Abstract:
The effects of nicorandil on vasodepressor responses to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P have been examined in anaesthetized rats. Intravenous bolus injections of VIP (0.3 microg kg(-1)), CGRP (0.1 microg kg(-1)) and substance P (0.1 microg kg(-1)) induced reductions of blood pressure accompanied by slight increases (less than 5%) in heart rate. Nicorandil infused intravenously at 10 or 30 microg kg(-1) min(-1) significantly augmented the vasodepressor responses to VIP and CGRP but did not modify the responses to substance P and acetylcholine (0.1 microg kg(-1)). Intravenous treatment with glibenclamide (20 mg kg(-1)) [corrected] significantly attenuated 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 rats, at least partly through ATP-sensitive K+-channel activation.