Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is mediated by calcitonin gene-related peptide.
Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning was studied in the isolated rat heart. The isolated rat heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 40 min after a 4-h hypothermic ischemic period. Heart rate, coronary flow, left ventricular pressure and the maximum value of the first derivatives of left ventricular pressure (+/-dp/dt(max)) were recorded, and plasma concentrations of CGRP-like immunoreactivity (CGRP-LI) and nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues, and creatine kinase in coronary effluent were measured. Delayed preconditioning was induced by i.v. injection of nitroglycerin 24 h before the experiment. Nitroglycerin (60 microg/kg or 120 microg/kg) caused an improvement of cardiac function, a decrease in the release of creatine kinase in coronary effluent and a decrease in the content of TNF-alpha in myocardial tissues. Nitroglycerin significantly increased plasma concentrations of CGRP and NO. After pretreatment with capsaicin, which depletes neurotransmitters in sensory nerves, or methylene blue, a selective guanylate cyclase inhibitor, the protection and the elevated release of CGRP induced by nitroglycerin were abolished. The present study suggests that improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is due to stimulation of CGRP release in the rat heart, and that the protection of CGRP-mediated nitroglycerin is related to inhibition of TNF-alpha production.
Zhou
Z H
ZH
Department of Pharmacology, Hunan Medical University, Changsha, 410078, Hunan, China.
Deng
H W
HW
Li
Y J
YJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000494:pharmacology*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000097:blood; D005996:Nitroglycerin / Q000008:administration & dosage*; D009926:Organ Preservation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002314:Cardioplegic Solutions; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009569:Nitric Oxide; D003402:Creatine Kinase; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide