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

摘要

Abstract Objective We investigated the acute effects of SIM on cerebral microvascular rarefaction and dysfunction in SHR s. Methods Male WKY and SHR s 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 SHR s 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 SHR s 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.