Vasodilatation induced by sinomenine lowers blood pressure in spontaneously hypertensive rats.
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).
Lee
Ping-Ying
PY
Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
Chen
Wency
W
Liu
I-Min
IM
Cheng
Juei-Tang
JT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D054086:KATP Channels; D009019:Morphinans; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; C009271:sinomenine; D005905:Glyburide; D016257:Fura-2