Previous studies have shown that
nitric oxide and
calcitonin gene-related peptide (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
nitric oxide-mediated delayed cardioprotection by brief intestinal
ischemia in rats. The serum concentration of
creatine kinase and
infarct size were measured after 45-min coronary artery occlusion and 180-min reperfusion. Ischemic preconditioning was induced by six cycles of 4-min
ischemia and 4-min reperfusion of the small intestine. Pretreatment with intestinal ischemic preconditioning for 24, 48, or 72 h significantly reduced
infarct size and
creatine kinase release, and the effects of ischemic preconditioning were completely 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-sensitive sensory nerves. Intestinal preconditioning caused a significant increase in plasma concentrations of CGRP, and the effect was also abolished by
L-NAME or
capsaicin. These results suggest that the delayed cardioprotection afforded by intestinal ischemic preconditioning is mediated by endogenous CGRP via the
nitric oxide pathway.