Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms  

作　　者：Tao SUN Rui LIU Yong-xiao CAO 

机构地区：[1]Department of Pharmacolgy, Xi-an Jiaotong University College of Medicine, Xi-an 710061, China

出　　处：《Acta Pharmacologica Sinica》2011年第8期1009-1018,共10页中国药理学报（英文版）

基　　金：Acknowledgements This study was supported by grant from the National Natural Science Foundation of China （No 30772566）.

摘　　要：Aim： To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods： Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results： Formononetin （1-300 μmol/L） elicited relaxation in arteries of the five regions that were pre-contracted by KCI （60 mmol/L）, U46619 （1 μmol/L） or phenylephrine （10 μmol/L）. The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME （100 μmol/L）. Under conditions of endothelium denudation, formononetin （10, 30, and 100 μmol/L） inhibited the contraction induced by KCI and that induced by CaCl2 in Ca^2＋-free depolarized medium. In the absence of extracellular Ca^2＋, formononetin （10, 30, and 100 μmol/L） depressed the constriction caused by phenylephrine （10 μmol/L）, but did not inhibit the tonic contraction in response to the addition of CaCl2 （2 mmol/L）. The contraction caused by caffeine （30 mmol/L） was not inhibited by formononetin （100 μmol/L）. Formononetin （10 and 100 μmol/L） reduced the change rate of Ca^2＋-fluorescence intensity in response to KCI （50 mmol/L）. In spontaneously hypertensive rats, formononetin （5, 10, and 20 mg/kg） slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion： Formononetin causes vasodilatation via two pathways： （1） endothetium-independent pathway, probably due to inhibition of voltage-dependent Ca^2＋ channels and intracellular Ca^2＋ release; and （2） endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.Aim： To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods： Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results： Formononetin （1-300 μmol/L） elicited relaxation in arteries of the five regions that were pre-contracted by KCI （60 mmol/L）, U46619 （1 μmol/L） or phenylephrine （10 μmol/L）. The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME （100 μmol/L）. Under conditions of endothelium denudation, formononetin （10, 30, and 100 μmol/L） inhibited the contraction induced by KCI and that induced by CaCl2 in Ca^2＋-free depolarized medium. In the absence of extracellular Ca^2＋, formononetin （10, 30, and 100 μmol/L） depressed the constriction caused by phenylephrine （10 μmol/L）, but did not inhibit the tonic contraction in response to the addition of CaCl2 （2 mmol/L）. The contraction caused by caffeine （30 mmol/L） was not inhibited by formononetin （100 μmol/L）. Formononetin （10 and 100 μmol/L） reduced the change rate of Ca^2＋-fluorescence intensity in response to KCI （50 mmol/L）. In spontaneously hypertensive rats, formononetin （5, 10, and 20 mg/kg） slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion： Formononetin causes vasodilatation via two pathways： （1） endothetium-independent pathway, probably due to inhibition of voltage-dependent Ca^2＋ channels and intracellular Ca^2＋ release; and （2） endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.

关 键 词：FORMONONETIN arterial rings VASODILATATION voltage-dependent Ca^2＋ channel intracellular Ca^2＋ release nitric oxide spontaneously hypertensive rats blood pressure 

分 类 号：Q463[生物学—生理学] TQ463.4[化学工程—制药化工]