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

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^-1 ) 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.

Keywords: intravital microscopy; laser speckle contrast imaging; microvascular rarefaction; pleiotropic effects; renin-angiotensin system; statins.