PT  - JOURNAL ARTICLE
AU  - Guei-Jane Wang
AU  - Xi-Chen Wu
AU  - Chieh-Fu Chen
AU  - Lie-Chwen Lin
AU  - Yi-Tsau Huang
AU  - Jie Shan
AU  - Peter K. T. Pang
TI  - Vasorelaxing Action of Rutaecarpine: Effects of Rutaecarpine on Calcium Channel Activities in Vascular Endothelial and Smooth Muscle Cells
DP  - 1999 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1237--1244
VI  - 289
IP  - 3
4099  - http://jpet.aspetjournals.org/content/289/3/1237.short
4100  - http://jpet.aspetjournals.org/content/289/3/1237.full
SO  - J Pharmacol Exp Ther1999 Jun 01; 289
AB  - 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 μg/kg i.v.) was significantly blocked by the nitric oxide synthase inhibitorNω-nitro-l-arginine. In aortic rings, Rut (0.1–3.0 μM)-induced vasorelaxation was inhibited byNω-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 μM) inhibited the norepinephrine-induced contraction generated by Ca2+ influx and at 1.0 μM 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 μM) elicited an opening of such channels. However, in VSMCs, Rut (10.0 μM) inhibited significantly the L-type voltage-dependent Ca2+ channels. In ECs cells, Rut (1.0, 10.0 μM) 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. The American Society for Pharmacology and Experimental Therapeutics