ROLES OF BRAIN ANGIOTENSIN-II AND C-TYPE NATRIURETIC PEPTIDE IN DEOXYCORTICOSTERONE ACETATE-SALT HYPERTENSION IN RATS

Objective. To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorti costerone acetate (DOCA)-salt hypertension. Methods. We injected 50 mu g/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmo l/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventr icular infusion of 1.5 mol/l NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were conti nuously recorded. Blood (2 ml) was collected at the end of the infusio n for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 mu g/kg per day CV-11974, 10 or 50 nmol/kg per da y CNP-22, or the vehicle (1 mu l/h) into the cerebral ventricles of DO CA-salt hypertensive rats for 7 days by using osmotic minipumps, and m easured their systolic arterial pressures, pulse rates, and urinary ex cretions of vasopressin. Results. Intracerebroventricular pre-administ rations of CV-11 974 and of CNP-22 inhibited increases in mean arteria l pressure, heart rate, and plasma vasopressin concentration induced b y intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induc ed by intracerebroventricular infusion of 1.5 mol/l NaCl were suppress ed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventr icular infusions of 50 mu g/kg per day CV-11974 attenuated hypertensio n in DOCA-salt treated rats, accompanied by a reduction in urinary exc retion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. Conc lusion. Brain angiotensin II could play a role in the presser mechanis m of DOCA-salt hypertension by increasing release of vasopressin via t ype 1 receptors, That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of thi s inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats. J Hype rtens 16:1175-1185. (C) 1998 Lippincott-Raven Publishers.