We examined the mechanisms underlying the
vasorelaxant effect of
dehydroevodiamine (DeHE), one of the bioactive components of the Chinese herbal
drug Evodia rutaecarpa that has been shown to produce
vasorelaxant and
hypotension. DeHE (10(-7)-10(-4) M) concentration-dependently relaxed isolated rat mesenteric arteries precontracted with
phenylephrine (PE). This
vasorelaxant potency was diminished by 15% by endothelial removal, L-NG-nitro
arginine, or
methylene blue (MB), but not
indomethacin treatment, indicating that the
vasorelaxant effect of DeHE was partially endothelium dependent and mediated by
nitric oxide (NO) and the
cyclic GMP pathway. In endothelium-denuded preparations, DeHE caused a rightward shift of the contractile concentration-response curve (CRC) to PE in a dose-dependent manner with a pA2 value of 6.15. Maximal response was unaffected. Receptor binding assay indicated that DeHE competed with alpha 1-adrenoceptor
ligand prazosin with a Ki value of 3.57 microM.
Potassium channel activity-attenuating conditions such as increased level of extracellular K+ (20 mM) and treatment with the antagonist
tetraethylammonium (
TEA) significantly inhibited DeHE's effect, suggesting a mode of action similar to that of a
potassium channel activator. In addition, high concentrations of DeHE (3 x 10(-5) and 10(-4) M) relaxed high K+ (80 mM)-evoked contraction, indicating that DeHE might possess K+ channel blocking properties. Multiple-action mechanisms, including endothelium dependence, alpha 1-adrenoceptor blockade, K+ channel activation, and Ca2+ channel blockade were probably involved in the
vasorelaxant effects of DeHE.