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 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.