On the mechanism of the protective effects of nitroglycerin and nicorandilin cardiac anaphylaxis

Previous investigations have shown that nitric oxide donors and nicorandil can suppress allergic reaction. In the present study, the protective effect s of nitroglycerin and nicorandil on cardiac anaphylaxis were examined. Pre sensitized guinea-pig hearts challenged with specific antigen caused a mark ed decrease in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/- dp/dt(max)), increase in heart rate, and prolongation of P -R interval. Nitroglycerin (300 nM) or nicorandil (100 muM) markedly increa sed the content of calcitonin gene-related peptide (CGRP) concomitant with a significant improvement of the cardiac dysfunction and alleviation of the extension of P-R interval. Nicorandil at a concentration of 100 muM also i nhibited the sinus tachycardia and histamine release. The protection afford ed by nitroglycerin was abolished by glibenclamide, a blocker of ATP-sensit ive potassium channels, or by CGRP(8-37), the selective CGRP receptor antag onist, or by pretreatment with capsaicin, which depletes endogenous CGRP. T he inhibitory effect of nicorandil on cardiac anaphylaxis was abolished onl y by glibenclamide but not by pretreatment with capsaicin. These results su ggest that nitroglycerin and nicorandil possess a protection of cardiac ana phylactic injury. The present study also suggests that the protective effec t of nitroglycerin may be related to stimulation of CGRP release and openin g the K-ATP channel, and that the effect of nicorandil is mainly due to the activation of the K-ATP channel.