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2016 ; 11
(5
): 1748-1754
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Imperatorin derivative OW1 inhibits the upregulation of TGF-? and MMP-2 in
renovascular hypertension-induced cardiac remodeling
#MMPMID27168797
Zhou N
; Zhu Y
; Zhang P
; Zhang YU
; Zhou M
; Wang T
; He L
Exp Ther Med
2016[May]; 11
(5
): 1748-1754
PMID27168797
show ga
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-?1 (TGF-?1). 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-?(1) 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.