Vol. 289, Issue 3, 1237-1244, June 1999

Vasorelaxing Action of Rutaecarpine: Effects of Rutaecarpine on Calcium Channel Activities in Vascular Endothelial and Smooth Muscle Cells¹

Guei-Jane Wang, Xi-Chen Wu, Chieh-Fu Chen, Lie-Chwen Lin, Yi-Tsau Huang, Jie Shan and Peter K. T. Pang

National Research Institute of Chinese Medicine, Taipei Taiwan, Republic of China (G.J.W., C.F.C., L.C.L.); Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China (Y.T.H.); and Department of Physiology, University of Alberta, Edmonton, Alberta, Canada (X.C.W., J.S., P.K.T.P.)

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 inhibitor N-nitro-L-arginine. In aortic rings, Rut (0.1-3.0 µM)-induced vasorelaxation was inhibited by N-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.