Vasodilatation Induced by Sinomenine Lowers Blood Pressure in Spontaneously Hypertensive Rats

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).

Role of Musclin in the Pathogenesis of Hypertension in Rat

“…The intracellular signals linked with the NPR-C receptor have been demonstrated in cardiovascular tissues and cells [11]. Recently, it has been reported that ANP interacts with NPR-C in atria, ventricles, and the aorta to activate Ca 2+ -loaded calmodulin and endothelial nitric oxide synthase (eNOS) through the Gi protein [12].…”

“…The changes in the intracellular calcium concentration were detected using the fluorescent probe fura-2 [11]. A7r5 cells were placed in buffered physiological saline solution (PSS) containing 140 mM NaCl, 5.9 mM KCl, 1.2 mM CaCl 2 , 1.4 mM MgCl 2 , 11.5 mM glucose, 1.8 mM Na 2 HPO 4 , and 10 mM Hepes-Tris; next, 5 µM fura-2 was added to this solution; and then, the cells were incubated for 1 h in humidified atmosphere containing 5% CO 2 and 95% air at 37° C. The cells were washed and incubated for further 30 min in PSS.…”

Characterization of preptin-induced insulin secretion in pancreatic β-cells

“…The changes in the intracellular calcium concentration were detected using the fluorescent probe fura-2 (Lee et al 2007). Min 6 cells were placed in buffered physiological saline solution containing 140 mM NaCl, 5 .…”

SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice

“…Sinomenine, a natural alkaloid, was isolated from the roots of Sinomenium acutum, and a variety of bioactivities have been reported, such as inhibition of the growth of several cancers [14][15][16][17][18], dilation of vascular to lower pressure [19], blocking tissue modeling after chronic cardiac allograft rejection [20], anti-angiogenesis [21] and anti-inflammation [22][23][24]. Due to its anti-inflammatory and antirheumatic effects, sinomenine has been employed clinically for the treatment of RA in China for a long time [25,26].…”