Role of calcitonin gene-related peptide in prostaglandins-mediated ischemic preconditioning in guinea pig hearts

AIM: To examine the role of calcitonin gene-related peptide (CGRP) in ische mic preconditioning induced by prostaglandins in isolated guinea pig hearts . METHODS: The isolated guinea pig hearts were perfused in a Langendorff mo del. The heart rate, coronary flow, left ventricular pressure, and its firs t derivatives (+/- dp/ dt(max)) were recorded and die calcitonin gene-relat ed peptide-like immunoreactivity (CGRP-LI) and 6-keto-PGF(1 alpha) were mea sured. RESULTS: Endothelin-1 (200 pmol in 1 mL K-H buffer) reduced the left ventricular developed pressure and its first derivatives (+/- dp/dt(max)), heart rate, and coronary flow. Preconditioning with two cycles of 5-min gl obal ischemia and 5-min reperfusion attenuated endothelin-1-induced myocard ial injury, and concentrations of both CGRP and 6-keto-PGF(1 alpha), in the coronary effluent were markedly raised in the preconditioning periods. Pre treatment with capsaicin, which depletes endogenous CGRP, abolished the ele vated level of CGRP concomitantly with loss of the cardioprotection induced by ischemic preconditioning. CGRP(8-37) (100 nmol/L), a selective CGRP(1) receptor antagonist, also abolished the protective effects of ischemic prec onditioning. After pretreatment with indometacin (10 mu mol/L), an inhibito r of cyclooxygenase, the protective effects of ischemic preconditioning wer e abolished and the release of 6-keto-PGF(1 alpha) was no longer elevated. Pretreatment with indometacin abolished the elevated level of CGRP in the c oronary effluent. CONCLUSION: Endogenous prostaglandins are involved in the protective effects of ischemic preconditioning, and the beneficial effects of prostaglandins are mediated by CGRP in the guinea pig heart.