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急性辛伐他汀治疗可恢复原发性高血压模型中脑功能性毛细血管密度,并减轻血管紧张素II诱导的微循环变化。

Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II-induced microcirculatory changes in a model of primary hypertension.

作者信息

Freitas Felipe, Estato Vanessa, Reis Patricia, Castro-Faria-Neto Hugo C, Carvalho Vinícius, Torres Rafael, Lessa Marcos A, Tibirica Eduardo

机构信息

Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.

Laboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.

出版信息

Microcirculation. 2017 Nov;24(8). doi: 10.1111/micc.12416.

DOI:10.1111/micc.12416
PMID:28865157
Abstract

OBJECTIVE

We investigated the acute effects of SIM on cerebral microvascular rarefaction and dysfunction in SHRs.

METHODS

Male WKY and SHRs were divided into 4 groups of 8 animals each: WKY-CTL and SHR-CTL, treated with 0.9% saline; and WKY+SIM and SHR+SIM, treated with SIM (30 mg/kg/d) for 3 days by gavage. Cerebral FCD was assessed by intravital fluorescence videomicroscopy. mCBF before and after administration within the cranial window of angiotensin II (1 μmol L ) was investigated using laser speckle contrast imaging.

RESULTS

Cerebral FCD was reduced in SHR-CTL compared to WKY-CTL (P < .05). SIM increased cerebral FCD in SHRs compared to SHR-CTL (P < .05). The mCBF was reduced in SHR-CTL compared to WKY-CTL (P < .05), and SIM increased mCBF compared with SHR-CTL (P < .05). Angiotensin II elicited a reduction of mCBF in SHR-CTL and increased mCBF in WKY-CTL (SHR-CTL -13.53 ± 2% vs WKY-CTL +13.74 ± 4%; P < .001), which was attenuated in SHRs treated with SIM (SHR+SIM -6.7 ± 1% vs SHR-CTL -13.53 ± 2%; P < .01).

CONCLUSIONS

The antihypertensive effect of SIM is associated with an improvement in cerebral microvascular perfusion and capillary density that may help to prevent hypertension-induced cerebrovascular damage independent of cholesterol-lowering.

摘要

目的

我们研究了西尼地平(SIM)对自发性高血压大鼠(SHRs)脑微血管稀疏和功能障碍的急性影响。

方法

将雄性Wistar-Kyoto大鼠(WKY)和SHRs分为4组,每组8只动物:WKY-CTL和SHR-CTL组,给予0.9%生理盐水;WKY+SIM和SHR+SIM组,通过灌胃给予SIM(30mg/kg/d),持续3天。采用活体荧光视频显微镜评估脑血流动力学(FCD)。使用激光散斑对比成像研究在血管紧张素II(1μmol/L)颅窗内给药前后的脑血流量(mCBF)。

结果

与WKY-CTL组相比,SHR-CTL组的脑FCD降低(P<0.05)。与SHR-CTL组相比,SIM增加了SHRs的脑FCD(P<0.05)。与WKY-CTL组相比,SHR-CTL组的mCBF降低(P<0.05),与SHR-CTL组相比,SIM增加了mCBF(P<0.05)。血管紧张素II使SHR-CTL组的mCBF降低,使WKY-CTL组的mCBF增加(SHR-CTL组为-13.53±2%,WKY-CTL组为+13.74±4%;P<0.001),在用SIM治疗的SHRs中这种情况减弱(SHR+SIM组为-6.7±1%,SHR-CTL组为-13.53±2%;P<0.01)。

结论

SIM的降压作用与脑微血管灌注和毛细血管密度的改善有关,这可能有助于预防高血压引起的脑血管损伤,且与降低胆固醇无关。

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