Imperatorin derivative OW1 inhibits the upregulation of TGF-β and MMP-2 in renovascular hypertension-induced 
cardiac remodeling

Zhou,Nan; Zhu,Yaning; Zhang,Peng; Zhang,Yu; Zhou,Mingyao; Wang,Tao; He,Langchong

doi:10.3892/etm.2016.3172

Imperatorin derivative OW1 inhibits the upregulation of TGF-β and MMP-2 in renovascular hypertension-induced cardiac remodeling

Authors:
- Nan Zhou
- Yaning Zhu
- Peng Zhang
- Yu Zhang
- Mingyao Zhou
- Tao Wang
- Langchong He
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Affiliations: Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Institute of Material Medica, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Xi'an Medical Emergency Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: March 15, 2016 https://doi.org/10.3892/etm.2016.3172
Pages: 1748-1754
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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‑β1 in 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.

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