Delayed cardioprotection by intestinal preconditioning is mediated by calcitonin gene-related peptide

Previous studies have shown that nitric oxide and calcitonin gene-related p eptide (CGRP) are involved in mediation of the delayed cardioprotection of ischemic or pharmacological preconditioning, and nitric oxide can evoke the release of CGRP. In the present study, we examined the role of CGRP in nit ric oxide-mediated delayed cardioprotection by brief intestinal ischemia in rats. The serum concentration of creatine kinase and infarct size were mea sured after 45-min coronary artery occlusion and 180-min reperfusion. Ische mic preconditioning was induced by six cycles of 4-min ischemia and 4-min r eperfusion of the small intestine. Pretreatment with intestinal ischemic pr econditioning for 24, 48, or 72 It significantly reduced infarct size and c reatine kinase release, and the effects of ischemic preconditioning were co mpletely abolished by L-nitroarginine methyl ester (L-NAME, 10 mg/kg, i.p.) , an inhibitor of nitric oxide synthase, or by pretreatment with capsaicin (50 mg/kg, s.c.), which selectively depletes transmitters in capsaicin-sens itive sensory nerves. Intestinal preconditioning caused a significant incre ase in plasma concentrations of CGRP. and the effect was also abolished by L-NAME or capsaicin. These results suggest that the delayed cardioprotectio n afforded by intestinal ischemic preconditioning is mediated by endogenous CGRP via the nitric oxide pathway. (C) 2001 Published by Elsevier Science B.V.