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

Abstract

We investigated the acute effects of SIM on cerebral microvascular rarefaction and dysfunction in SHRs. 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 (30mg/kg/d) for 3days by gavage. Cerebral FCD was assessed by intravital fluorescence videomicroscopy. mCBF before and after administration within the cranial window of angiotensin II (1μmol L-1 ) was investigated using laser speckle contrast imaging. 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). 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.