The Depressor and Vasodilator Effects of Rutaecarpine are Mediated by Calcitonin Gene-Related Peptide

Abstract

Previous studies have shown that rutaecarpine has depressor and vasodilator effects, and activates vanilloid receptors to evoke calcitonin gene-related peptide (CGRP) release. In the present study, we examined whether the depressor and vasodilator effects of rutaecarpine are related to the stimulation of endogenous CGRP release via activation of vanilloid receptors in rats. Rutaecarpine (30, 100, or 300 μg/kg, i. v.) caused a depressor effect concomitantly with an increase in the plasma concentrations of CGRP in a dose-dependent manner, and the effects of rutaecarpine were abolished by pretreatment with capsaicin (50 mg/kg, s. c.) which depletes neurotransmitters in sensory nerves. In aortic and superior mesenteric arterial rings, rutaecarpine (10 ^{- 7} - 10 ^{- 5} M) or capsaicin (3 × 10 ^{- 9} - 3 × 10 ^{- 6} M) caused a concentration-dependent vasodilator response, which was significantly attenuated by capsazepine (10 ^{- 5} M), a competitive vanilloid receptor antagonist, or by CGRP-(8 - 37) (10 ^{- 6} M), a selective CGRP receptor antagonist. After pretreatment with capsaicin (10 ^{- 5} M) for 20 min, vasodilator responses to rutaecarpine were also markedly attenuated. Similarly, pretreatment with rutaecarpine (10 ^{- 5} M) for 20 min also attenuated vasodilator responses to capsaicin. These results suggest that the depressor and vasodilator effects of rutaecarpine are related to stimulation of endogenous CGRP release via activation of vanilloid receptors in rats.

Key words

Evodia rutaecarpa - Rutaceae - rutaecarpine - calcitonin gene-related peptide - vanilloid receptor - capsaicin - rat

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