title: Imperatorin derivative OW1 inhibits the upregulation of TGF-β and MMP-2 in renovascular hypertension-induced cardiac remodeling.
abstract: Chronic hypertension induces vascular and cardiac remodeling. OW1 is a novel imperatorin derivative that was previously reported to inhibit vascular remodeling and improve kidney function affected by hypertension. In the present study, the effect of OW1 on the cardiac remodeling induced by hypertension was investigated. OW1 inhibited vascular smooth muscle cell (VSMC) proliferation and the phenotypic modulation of VSMCs induced by angiotensin II (Ang II). The OW1-induced vasodilatation of rat cardiac arteries was evaluated in vitro. Renovascular hypertensive rats were developed using the two-kidney one-clip method and treated with OW1 (40 or 80 mg/kg/day) or nifedipine (30 mg/kg per day) for 5 weeks. OW1 markedly reduced the systolic and diastolic blood pressure compared with that in the hypertension group or the respective baseline value during the first week. OW1 also reduced cardiac weight, and the concentrations of Ang II, aldosterone and transforming growth factor-β1 (TGF-β1). Histological examination demonstrated that OW1 exerted an inhibitory effect on vascular and cardiac remodeling. These inhibitory effects were associated with decreased cardiac levels of Ang II, matrix metalloproteinase-2 and TGF-β1in the hypertensive rats. In summary, OW1 exhibited a clear antihypertensive effect. More importantly, it inhibited vascular and cardiovascular remodeling, which may reduce the risk of hypertension-induced cardiovascular diseases. These results have potential implications in the development of new antihypertensive drugs.
authors.affiliation: Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Material Medica, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Zhang
authors.affiliation: Xi'an Medical Emergency Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Institute of Material Medica, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Material Medica, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Langchong
authors.initials: L
authors.lastname: He
keywords: OW1; blood pressure; cardiac remodeling; imperatorin derivative; two-kidney one-clip hypertensive rats