Haemodynamic mechanisms of corticotropin (ACTH)-induced hypertension in the rat

Objectives To investigate the roles of cardiac output and systemic and regi onal resistances in corticotropin (ACTH)induced hypertension in the rat. Methods This study consisted of three series of experiments with eight grou ps of male Sprague-Dawley rats (n = 132). Series 1 comprised groups 1-4, wh ere 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 + A CTH treatments. Series 2 comprised groups 5 and 6, where group 5 = minoxidi l + sham and group 6 = minoxidil + ACTH treatments. Series 3 comprised grou ps 7 and 8, where group 7 = ramipril + sham and group 8 = ramipril + ACTH t reatments. Systolic blood pressure, water and food intakes, urine volume, a nd body weight were measured every second day. After 10 days of treatment, mean arterial blood pressure was measured by intra-arterial cannulation, an d cardiac output (CO), and renal, mesenteric and hindquarter blood flows (R BF, MBF and HBF) determined using transonic small animal flowmeters. Results ACTH 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 af fect total peripheral resistance (TPR), Atenolol blocked the rise in CO wit hout affecting the rise in blood pressure produced by ACTH treatment Minoxi dil lowered TPR, but did not prevent the rise in blood pressure or renal va scular resistance, Ramipril blunted the rise in RVR and blood pressure with out significantly affecting TPR. Conclusion Neither preventing rise in CO nor lowering TPR altered the ACTH- induced rise in blood pressure in the rat However, both the hypertension an d 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. J Hypertens 1999, 17:1715-1723 (C) Lippincott Williams & Wilkins.