Protective Effects of Rutaecarpine in Cardiac Anaphylactic Injury is Mediated by CGRP

Abstract

Previous investigations have indicated that rutaecarpine activates the vanilloid receptor to evoke calcitonin gene-related peptide (CGRP) release. CGRP has been shown to alleviate cardiac anaphylactic injury. In the present study, the effect of rutaecarpine on cardiac anaphylaxis was examined. Challenge of presensitized guinea-pig hearts with a specific antigen caused marked decreases in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (± dp/dt_max), an increase in heart rate, and prolongation of the P-R interval. Rutaecarpine (0.3 or 1 μM) markedly increased the content of calcitonin gene-related peptide (CGRP) in the coronary effluent and decreased the content of tumor necrosis factor-α (TNF-α) in myocardial tissues concomitantly with a significant improvement of cardiac function and alleviation of the extension of the P-R interval. Rutaecarpine at the concentration of 1 μM also inhibited the sinus tachycardia. The protective effects of rutaecarpine on cardiac anaphylaxis were abolished by CGRP_{8 - 37}, a selective CGRP receptor antagonist. These results suggest that the protective effects of rutaecarpine on cardiac anaphylactic injury are related to inhibition of TNF-α production by stimulation of CGRP release.

Key words

Cardiac anaphylaxis - calcitonin gene-related peptide (CGRP) - rutaecarpine - tumor necrosis factor-α (TNF-α) - guinea-pig

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