title: Vasorelaxing action of rutaecarpine: effects of rutaecarpine on calcium channel activities in vascular endothelial and smooth muscle cells.
abstract: Rutaecarpine (Rut) has been shown to induce hypotension and vasorelaxation. In vitro studies indicated that the vasorelaxant effect of Rut was largely endothelium-dependent. We previously reported that Rut increased intracellular Ca2+ concentrations ([Ca2+]i) in cultured rat endothelial cells (ECs) and decreased [Ca2+]i in cultured rat vascular smooth muscle (VSMCs) cells. The present results showed that the hypotensive effect of Rut (10-100 microgram/kg i.v.) was significantly blocked by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine. In aortic rings, Rut (0. 1-3.0 microM)-induced vasorelaxation was inhibited by Nomega-nitro-L-arginine and hydroquinone but not by antagonists of the various K+ channels, 4-aminopyridine, apamin, charybdotoxin, or glibenclamide. Rut (0.1 and 1.0 microM) inhibited the norepinephrine-induced contraction generated by Ca2+ influx and at 1.0 microM increased cyclic GMP (cGMP) production in endothelium-intact rings and to a lesser extent in endothelium-denuded rings. In whole-cell patch-clamp recording, nonvoltage-dependent Ca2+ channels were recorded in ECs and Rut (0.1, 1.0 microM) elicited an opening of such channels. However, in VSMCs, Rut (10.0 microM) inhibited significantly the L-type voltage-dependent Ca2+ channels. In ECs cells, Rut (1.0, 10.0 microM) increased nitric oxide release in a Ca2+-dependent manner. Taken together, the results suggested that Rut lowered blood pressure by mainly activating the endothelial Ca2+-nitric oxide-cGMP pathway to reduce smooth muscle tone. Although the contribution seemed to be minor in nature, inhibition of contractile response in VSMCs, as evidenced by inhibition of Ca2+ currents, was also involved. Potassium channels, on the other hand, had no apparent roles.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei Taiwan, Republic of China. jenny@cma23.nricm.edu.tw
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: X C
authors.initials: XC
authors.lastname: Wu
authors.forename: C F
authors.initials: CF
authors.lastname: Chen
authors.forename: L C
authors.initials: LC
authors.lastname: Lin
authors.forename: Y T
authors.initials: YT
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Shan
authors.forename: P K
authors.initials: PK
authors.lastname: Pang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D052999:Quinazolinones
chemical_list: D015761:4-Aminopyridine; D000470:Alkaloids; D002118:Calcium; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D006152:Cyclic GMP; D006873:Hydroquinones; D026121:Indole Alkaloids; D019335:Nitroarginine; D009638:Norepinephrine; D026902:Potassium Channel Blockers; D011799:Quinazolines; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones; C031927:hydroquinone