The mechanism of the vasodilator effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa.
The mechanisms underlying the rutaecarpine-induced vasodilatation were studied using isolated rat mesenteric arterial ring segments. The results showed that rutaecarpine (0.1 microM to 0.1 mM) produced a dose-dependent vasorelaxing response in our preparations, which were precontracted with phenylephrine. This vasodilator effect was significantly attenuated by removal of the endothelium, treatment with L-NG-nitro-arginine, a nitric oxide synthase inhibitor, and methylene blue, a guanylyl cyclase inhibitor, but not by treatment with atropine, triprolidine and yohimbine. Rutaecarpine pretreatment (1 microM to 0.1 mM) reduced both the phasic (fast) and tonic (slow) phases of phenylephrine-induced contractions, suggesting that a reduction in intracellular calcium might be involved. It is thus concluded that while the vasorelaxing effect of rutaecarpine appeared to be endothelium-dependent and to involve nitric oxide and guanylyl cyclase, neither muscarinic receptors, histamine H1 receptors nor alpha 2-adrenoceptors are involved. Moreover, a direct effect on the vascular smooth muscle cell, possibly through a reduction in intracellular Ca2+, can not be excluded.
Chiou
W F
WF
National Research Institute of Chinese Medicine, Taipei, Hsien, Taiwan.
Chou
C J
CJ
Liao
J F
JF
Sham
A Y
AY
Chen
C F
CF
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D014311:Triprolidine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology; D052999:Quinazolinones
D000109:Acetylcholine; D000470:Alkaloids; D001120:Arginine; D001285:Atropine; D002118:Calcium; D026121:Indole Alkaloids; D008751:Methylene Blue; D019335:Nitroarginine; D010656:Phenylephrine; D011799:Quinazolines; D014311:Triprolidine; D015016:Yohimbine; C028632:rutecarpine; D052999:Quinazolinones