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.
Footnotes
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Send reprint requests to: Prof. Chieh-Fu Chen, National Research Institute of Chinese Medicine, No. 155-1, Section 2, Li-Nong Street, Pei-tou District (112), Taipei, Taiwan, Republic of China. E-mail: jennyw{at}cma23.nricm.edu.tw
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↵1 This work was supported by Grants NSC87-2314-B077-001 from the National Science Council of the Republic of China (to C.F.C.).
- Abbreviations:
- Rut
- rutaecarpine
- EC
- endothelial cell
- VSMC
- vascular smooth muscle cell
- NO
- nitric oxide
- l-NNA
- Nω-nitro-l-arginine
- NE
- norepinephrine
- VDCC
- voltage-dependent Ca2+ channel
- KCa
- Ca2+-dependent K+
- Kv
- voltage-dependent K+
- MAP
- mean arterial pressure
- FCS
- fetal calf serum
- HBSS
- Hanks’ balanced salt solution
- ROCC
- receptor-operated Ca2+ channel
- I-V
- current voltage
- Received June 29, 1998.
- Accepted January 28, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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