title: Antihypertensive effect of formononetin through regulating the expressions of eNOS, 5-HT2A/1B receptors and α1-adrenoceptors in spontaneously rat arteries.
abstract: One of the main pathological changes of hypertension is the dysfunction of blood vessels. We have found in our previous study that formononetin, one kind of phytoestrogens, has an acute antihypertensive effect. Therefore, we hypothesized that formononetin might produce a chronic antihypertensive effect through regulating the expressions of contractile receptors and endothelial nitric oxide synthase (eNOS) in artery. The present study was conducted to verify this effect. Male spontaneously hypertensive rats (SHRs) were divided into two groups, orally administrated formononetin (50mg/kg per day) and Tween 80 vehicle, respectively, for 8 weeks. The blood pressure was measured by tail-cuff method. Isometric tension of arterial rings was recorded by a myograph system. The mRNA and protein expression in arteries was determined with quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Results showed that the systolic blood pressure of SHRs decreased significantly in formononetin group compared to Tween 80 group. The vasoconstriction induced by phenylephrine or 5-hydroxytryptamine (5-HT) in the mesenteric artery segments in formononetin group was decreased, and the relaxation induced by acetylcholine was increased compared with that in Tween 80 group. In the mesenteric arteries of the formononetin-treated SHRs, the expressions of α(1)-adrenoceptors and 5-HT(2A/1B) receptors at both mRNA and protein levels decreased, while the mRNA and protein expressions of eNOS increased. In conclusion, formononetin has a chronic antihypertensive effect in SHRs. The antihypertensive mechanism may be associated with the down-regulation of α(1)-adrenoceptors and 5-HT(2A/1B) receptors, and the up-regulation of eNOS expression in arteries.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Lin-Hong
authors.initials: LH
authors.lastname: Huang
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011136:Polysorbates / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D060888:Real-Time Polymerase Chain Reaction; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D007529:Isoflavones; D011136:Polysorbates; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; C007768:formononetin; D052250:Nitric Oxide Synthase Type III