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TRANSLATIONAL PHYSIOLOGY

Chronic angiotensin II AT₁ receptor blockade increases cerebral cortical microvessel density

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 10 November 2004 ; accepted in final form 21 September 2005

Angiotensin II is known to stimulate angiogenesis in the peripheral circulation through activation of the angiotensin II type 1 (AT₁) receptor. This study investigated the effect of angiotensin receptor blockade on cerebral cortical microvessel density. Rats (6–7 wk old, n = 5–17) were instrumented with femoral arterial and venous indwelling catheters for arterial blood pressure measurement and drug administration. Rats were treated for 3 or 14 days with the AT₁ receptor blocker losartan (50 mg/day in drinking water) or vehicle. Brains were sectioned and immunostained for CD31, and microvessel density was measured. Treatment with losartan for 3 or 14 days resulted in a slight decrease in mean arterial blood pressure (3 days, 92 ± 1 mmHg; and 14 days, 99 ± 2 mmHg) compared with vehicle (109 ± 3 and 125 ± 4 mmHg, respectively). A furosemide + captopril 14-day treatment group was added to control for the blood pressure change (96 ± 3 mmHg). Microvessel density increased in groups treated with losartan for 14 days (429 ± 13 vessels/mm²) compared with vehicle (383 ± 11 vessels/mm²) but did not change with furosemide + captopril (364 ± 7 vessels/mm²). Thus AT₁ receptor blockade for 14 days resulted in increased cerebral microvessel density in a blood pressure-independent manner.

angiotensin receptor blockers; hypertension; microvascular growth

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