Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II-induced microcirculatory changes in a model of primary hypertension
2017
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.
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