Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

Abstract

Previous investigations have demonstrated that early preconditioning induced by nitroglycerin is mediated by calcitonin gene-related peptide (CGRP). In the present study, we addressed the question of whether delayed preconditioning induced by nitroglycerin in the rat is related to stimulation of the release and synthesis of CGRP. Sprague-Dawley rats were pretreated with nitroglycerin 24 h before the experiment. The left main coronary artery was occluded for 60 min, followed by 3 h reperfusion. Infarct size, serum creatine kinase activity, serum levels of NO and CGRP and the expression of alpha- and beta-CGRP isoform mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (60 or 120 microg/kg i.v.) reduced both the infarct size and the release of creatine kinase during reperfusion and caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitantly with an increase in concentrations of NO and CGRP. The increase in CGRP expression preceded the increase in CGRP release. The effects of nitroglycerin were abolished completely by pretreatment with methylene blue (30 mg/kg i.p.), an inhibitor of guanylate cyclase, or capsaicin (50 mg/kg s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. The present results suggest that the delayed cardioprotection induced by nitroglycerin is mediated mainly by the alpha-CGRP isoform via the NO-cGMP pathway.

Delayed anti-arrhythmic effect of nitroglycerin in anesthetized rats: Involvement of CGRP, PKC and mKATP channels

“…Using capsaicin to deplete sensory nerves from CGRP, we showed that the induction of late anti-infarct and anti-arrhythmic effects of NTG is CGRP dependent. Zhou et al also observed a similar anti-infarct effect in the same animal model [17]. CGRP could lead to PKC translocation [15,26] so we hypothesized that NTG may trigger the late phase through PKC activation and the late phase will be abolished using PKC inhibiter, CHE.…”

“…Group 2 (NTG, n = 11), rats received only NTG [120 μg kg − 1 , iv (2 μg kg − 1 min − 1 iv over 1 h)] [13,17]. Group 3 (CHE + NTG, n = 11), rats received CHE (5 mg kg − 1 , iv), 10 min before NTG infusion.…”

Nitroglycerin Protects Small Intestine from Ischemia–Reperfusion Injury via NO–cGMP Pathway and Upregulation of α-CGRP

“…Previous reports had shown that NO participated in delayed cardioprotection via a cGMP-dependent mechanism. 35,36 In the present experiment, MB, an inhibitor of guanylate cyclase, was used to investigate the role of NO-dependent activation of guanylate cyclase in the delayed preconditioning induced by NTG in rat small intestine. The results revealed that in vivo pretreatment with NTG caused not only an increase in blood concentrations of both CGRP and NO but also the CGRP mRNA expression.…”

Myocardial Ischemia-Reperfusion/Injury

“…Rats were allocated into 4 groups: a-Control group, non-treated , b-GTN-treated group, rats received GTN intraperitoneal 25 minutes before sacrifice, in a dose of 120 μg/kg bw (Zhou et al, 2002) ,cVit E-treated group, rat received vitamin E by oral tubal feeding 16-20 hours before sacrifice, in a dose of 250mg/rat d-Vit E and GTN-treated group, rats received vitamin E and GTN as in both GTN-treated group and vit E -treated group.…”