Involvement of calcitonin gene-related peptide in nitroglycerin induced improvement of preservation with cardioplegic solution.
OBJECTIVE
To study improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of calcitonin gene-related peptide (CG RP) release.


METHODS
The isolated rat heart was arrested using St Thomas Hospital cardioplegic solution and then was reperfused with normothermic Krebs-Henseleit solution for 40 min after the 4-h hypothermic ischemic period. Hear t rate, coronary flow, left ventricular pressure (LVP), and its first derivative (+/- dp/dtmax) were recorded, and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and the release of creatine kinase (CK) were measured.


RESULTS
Nitroglycerin (0.1 or 1 micro;mol/L) or CGRP (5 or 10 nmol/L) caused an improvement of cardiac function (LVP and +/- dp/dtmax) and a decrease in the release of creatine kinase during reperfusion. The protection induced by nitroglycerin was abolished by CGRP(8-37), the selective CGRP receptor antagonist, or pretreatment wit h capsaicin to deplete sensory nerves neurotransmitter content, but was unaltered by treatment w ith glibenclamide, the blocker of the ATP-sensitive potassium channel (KATP). The protection induced by exogenous CGRP was not also blocked by glibenclamide. Levels of CGRP-LI in the coronary effluent were significantly increased in the hearts treated with nitroglycerin. However, the elevated level of CGRP-LI by nitroglycerin was abolished by pretreatment with capsaicin.


CONCLUSIONS
The improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of CGRP release in the rat heart, and the effect is not related to the activation of the KATP channel.
Zhou
Z H
ZH
Department of Pharmacology, Hunan Medical University, Changsha 410078, China.
Deng
H W
HW
Li
Y J
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002314:Cardioplegic Solutions; D003402:Creatine Kinase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006334:Heart Function Tests / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002314:Cardioplegic Solutions; D010446:Peptide Fragments; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D003402:Creatine Kinase; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide