Previous investigations have indicated that the pharmacological activities of
evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with the stimulation of
calcitonin gene-related peptide (CGRP) release and that CGRP protects the myocardium against
ischemia-reperfusion injury. In the present study, we have examined whether
evodiamine protects against
myocardial ischemia-
reperfusion injury in rats and whether the protective effects of
evodiamine are related to the activation of
capsaicin-sensitive sensory nerves. Rats were pretreated with
evodiamine 10 min before the experiment, and then the left main coronary artery of rat hearts was subjected to 60 min occlusion followed by 180 min reperfusion.
Infarct size, the activity of serum
creatine kinase, serum concentrations of
TNF-alpha and plasma concentrations of CGRP were measured. Pretreatment with
evodiamine (30 or 60 microg/kg, i.v.) markedly increased the content of CGRP in plasma concomitantly with a significant reduction in
infarct size, the activity of serum
creatine kinase, and
TNF-alpha level, and the effects of
evodiamine were completely abolished by
capsazepine (5.0 mg/kg, s.c.), a competitive
vanilloid receptor antagonist. These results suggest that
evodiamine exerts a protection against
myocardial ischemia-
reperfusion injury in rats and that the protective effects of
evodiamine are related to stimulation of CGRP release via activation of
vanilloid receptors.