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 μM 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 μM 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 μM 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.

Key words

Evodia rutaecarpa - Rutaceae - rutaecarpine - calcitonin gene-related peptide - vanilloid receptor - capsaicin - guinea-pig isolated heart

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