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  • Title: Vasodilatation induced by sinomenine lowers blood pressure in spontaneously hypertensive rats.
    Author: Lee PY, Chen W, Liu IM, Cheng JT.
    Journal: Clin Exp Pharmacol Physiol; 2007 Oct; 34(10):979-84. PubMed ID: 17714082.
    Abstract:
    1. Sinomenine is an alkaloid with a wide range of pharmacological actions. In the present study, we investigated the effect of sinomenine on blood pressure and its possible mechanisms of action. 2. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were given intraperitoneal injections of sinomenine. At 30 min, 2.5-10 mg/kg sinomenine decreased systolic blood pressure (SBP) in a dose-dependent manner in SHR, but had no effect on the SBP in WKY rats. 3. The vascular effect of sinomenine was then examined in aortic rings isolated from Wistar rats. Sinomenine (0.1-10 micromol/L) produced concentration-dependent relaxation in aortic rings precontracted with phenylephrine (10 nmol/L) or KCl (40 mmol/L). Glibenclamide (1-100 micromol/L), a specific inhibitor of ATP-sensitive K(+) channels attenuated the sinomenine-induced relaxation, but this effect was not observed when inhibitors of other types of K(+) channels were used. 4. We further investigated the effects of sinomenine on changes in intracellular Ca(2+) concentrations ([Ca(2+)](i)) in cultured aortic smooth muscle (A7r5) cells by using the Ca(2+)-sensitive dye fura-2 as an indicator. Sinomenine, over the concentration range 0.1-10 micromol/L, decreased the increases in [Ca(2+)](i) elicited by phenylephrine (1 micromol/L) or KCl (40 mmol/L) in a concentration-dependent manner. Glibenclamide (1-100 micromol/L) abolished the effects of sinomenine. 5. In conclusion, sinomenine causes vascular relaxation by opening ATP-sensitive K(+) channels, thus decreasing [Ca(2+)](i).
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