Angiotensin Type 2 Receptor Agonist Compound 21 Reduces Vascular Injury and Myocardial Fibrosis in Stroke-Prone Spontaneously Hypertensive Rats

—Angiotensin type 2 receptor–mediated effects of angiotensin II appear to counteract many of the effects mediated via the angiotensin type 1 receptor. Compound 21 (C21), a selective angiotensin type 2 receptor agonist, has demonstrated beneficial effects on cardiac function after myocardial infarction in rodents. We hypothesized that C21 alone or in combination with an angiotensin type 1 receptor antagonist would blunt the development of hypertension and vascular damage in stroke-prone spontaneously hypertensive rats. Six-week–old stroke-prone spontaneously hypertensive rats received C21 (1 mg/kg per day), the angiotensin type 1 receptor antagonist losartan (10 mg/kg per day), C21 plus losartan, or vehicle PO for 6 weeks. Systolic blood pressure was lower in losartan and C21-losartan combination groups (P