Cerebral microvascular dysfunction in angiotensin II‐induced hypertension

Abstract

Inflammation has been implicated in the pathogenesis of hypertension. Although hypertension is a major risk factor for ischemic stroke, and inflammation contributes to the pathogenesis of stroke, relatively little is known about the inflammatory effects of arterial hypertension in the cerebral microcirculation. The objective of this study was to determine whether angiotensin II (AngII)‐induced hypertension promotes blood cell‐endothelial cell adhesion in cerebral venules. Leukocyte and platelet adhesion were monitored in cerebral venules of C57Bl/6 mice via a cranial window. Hypertension was induced by subcutaneous implantation of an AngII‐loaded Alzet pump for a 2 wk period. Mice were placed on either a normal (ND) or high salt diet (HSD). AngII infusion induced a dose‐dependent (400–2000 ng/kg/min) increase in arterial pressure, which was higher in HSD mice. Mice on either ND or HSD exhibited an increased adhesion of both leukocytes and platelets at 600 ng/kg/min. Higher AngII doses did not elicit further increases in blood cell adhesion in ND mice, but further dose‐dependent increases were noted HSD mice. Blood brain barrier (BBB) permeability was increased by AngII in both ND and HSD mice. These findings indicate that the cerebral microcirculation assumes an inflammatory and pro‐thrombogenic phenotype in AngII‐induced hypertension, which may account for the accompanying BBB dysfunction. (HL26441)