TRANSLATIONAL PHYSIOLOGY Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density

Munzenmaier, Diane H., and Andrew S. Greene. Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density. Am J Physiol Heart Circ Physiol 290: H512–H516, 2006. First published September 30, 2005; doi:10.1152/ajpheart.01136.2004.—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/mm) compared with vehicle (383 11 vessels/mm) but did not change with furosemide captopril (364 7 vessels/mm). Thus AT1 receptor blockade for 14 days resulted in increased cerebral microvessel density in a blood pressure-independent manner.