Angiotensin II AT(1)-receptor blockade inhibits monocyte activation and adherence in transgenic (mRen2)27 rats

This study investigated whether angiotensin II AT(1)-receptor blockade with losartan inhibits endothelium-monocyte interactions originating from long- term activation of the renin-angiotensin system in hypertensive transgenic rats [TGR(mRen2)27]. The number of circulating activated monocytes, monocyt es adhered to thoracic aorta endothelium, and the extent of endothelial cel l injury were compared in adult male transgenic (mRen2)27 and age-matched H annover Sprague-Dawley (SD) rats after 12 days of continuous subcutaneous a dministration of saline (120 mu l/24 h), losartan (10 mg/kg/24 h), or the v asodilator hydralazine (3 mg/kg/24 h). At the doses administered in this ex periment, both losartan and hydralazine normalized mRen2 rat blood pressure s equal to values in similarly treated SD rats. Compared with saline infusi on, administration of either antihypertensive in mRen2 rats reduced (p < 0. 05) endothelial cell injury, but only losartan significantly (p < 0.05) dec reased the number of activated circulating and endothelium-adherent monocyt es. Infusion of antihypertensives in SD rats had no effect on blood pressur es, monocyte activity, or endothelial injury compared with saline administr ation. These findings suggest that the recruitment and infiltration of leuk ocytes into the subendothelium associated with renin-angiotensin system-ind uced hypertension is partly mediated by pressure-independent AT(1)-receptor pathways.