title: The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related-gene peptide through activation of vanilloid receptors in guinea-pig hearts.
abstract: Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects against myocardial ischemia-reperfusion injury and that rutaecarpine activates vanilloid receptors to evoke CGRP release. In the present study, we examined whether rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts, and whether the protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors. The isolated guinea-pig heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 30 min after a 4-h hypothermic ischemic period. Hypothermic ischemia caused a decline in cardiac function (left ventricular pressure, +/-dp/dt(max), heart rate and coronary flow) and an increased release of creatine kinase during reperfusion. Rutaecarpine at the concentration of 1.0 microM significantly improved the recovery of cardiac function and reduced the release of creatine kinase during reperfusion after hypothermic ischemia. Rutaecarpine at the concentration of 3.0 microM significantly reduced the release of creatine kinase and increased the coronary flow, but only caused a slight improvement of left ventricular pressure, +/-dp/dt(max), heart rate during reperfusion. The cardioprotective effects of rutaecarpine were abolished by capsazepine, a competitive vanilloid receptor antagonist, or by CGRP (8-37), a selective CGRP receptor antagonist. Rutaecarpine at the concentration of 1.0 or 3.0 microM significantly increased the release of CGRP, which was also abolished by capsazepine. These results suggest that rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and that the protective effects of rutaecarpine are due to stimulation of endogenous CGRP release via activating vanilloid receptors.
authors.affiliation: Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, P.R. China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.forename: Han-Wu
authors.initials: HW
authors.lastname: Deng
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D032086:Evodia / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D026121:Indole Alkaloids; D008297:Male; D015394:Molecular Structure; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010946:Plants, Medicinal / Q000737:chemistry; D011799:Quinazolines; D011863:Radioimmunoassay; D011955:Receptors, Drug / Q000378:metabolism*; D017725:Ventricular Pressure / Q000187:drug effects; D052999:Quinazolinones
chemical_list: D000470:Alkaloids; D015740:Calcitonin Gene-Related Peptide; D002316:Cardiotonic Agents; D003402:Creatine Kinase; D026121:Indole Alkaloids; D011799:Quinazolines; D011955:Receptors, Drug; C028632:rutecarpine; D052999:Quinazolinones