Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density.
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.
Munzenmaier
Diane H
DH
Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. dmunz@mcw.edu
Greene
Andrew S
AS
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development; D002216:Captopril / Q000494:pharmacology; D002540:Cerebral Cortex / Q000098:blood supply*; D004232:Diuretics / Q000494:pharmacology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005665:Furosemide / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D005665:Furosemide; D002216:Captopril; D019808:Losartan