ObjectivesTo investigate the roles of cardiac output and systemic and regional resistances in corticotropin (ACTH)- induced hypertension in the rat.MethodsThis study consisted of three series of experiments with eight groups of male Sprague-Dawley rats (n= 132). Series 1 comprised groups 1–4, where group 1 = sham (0.9% NaCl, subcutaneous (sc) injection); group 2 = ACTH (0.5 mg/kg per day, sc); group 3 = atenolol + sham; group 4 = atenolol + ACTH treatments. Series 2 comprised groups 5 and 6, where group 5 = minoxidil + sham and group 6 = minoxidil + ACTH treatments. Series 3 comprised groups 7 and 8, where group 7 = ramipril + sham and group 8 = ramipril + ACTH treatments. Systolic blood pressure, water and food intakes, urine volume, and body weight were measured every second day. After 10 days of treatment, mean arterial blood pressure was measured by intra-arterial cannulation, and cardiac output (CO), and renal, mesenteric and hindquarter blood flows (RBF, MBF and HBF) determined using transonic small animal flowmeters.ResultsACTH treatment increased blood pressure (P< 0.001) with a rise in CO (P< 0.01) and renal vascular resistance (RVR,P< 0.05), but did not affect total peripheral resistance (TPR). Atenolol blocked the rise in CO without affecting the rise in blood pressure produced by ACTH treatment. Minoxidil lowered TPR, but did not prevent the rise in blood pressure or renal vascular resistance. Ramipril blunted the rise in RVR and blood pressure without significantly affectingTPR.ConclusionNeither preventing rise in CO nor lowering TPR altered the ACTH-induced rise in blood pressure in the rat. However, both the hypertension and rise in RVR were prevented by ramipril. These data suggest that increase in RVR may play a role in the pathogenesis of ACTH-induced hypertension in the rat.