AT(1) RECEPTORS MEDIATE CHRONIC CENTRAL-NERVOUS-SYSTEM AII HYPERTENSION IN RATS FED HIGH SODIUM-CHLORIDE DIET FROM WEANING

CNS angiotensin II (AII) hypertension is induced by chronic, low dose intracerebroventricular (ICV) AII infusion only in rats raised on a re latively high sodium chloride diet (250 meg kg(-1) food) from weaning. This experimental model of hypertension is dependent upon renal sympa thetic innervation and associated with neurogenic sodium retention. Th is study determined whether AT(1) and/or AT(2) receptor subtypes in th e CNS mediate this neurogenic ICV AII hypertension. Rats were weaned a t 21 days of age and fed a 1.5% sodium chloride diet for 10-12 weeks. At adulthood, animals were instrumented with CNS lateral ventricular c annulas, femoral arterial and vein catheters and housed in metabolic p ens for chronic study. Low dose ICV AII infusion (20 ng min(-1)) incre ased mean arterial pressure by 12 +/- 2 mm Hg and decreased urinary so dium excretion for three consecutive days. Subsequent ICV AT(1) blocka de with losartan abolished both the presser and antinatriuretic respon ses to low dose ICV AII. In contrast, ICV AT(2) receptor blockade with PD 123319 did not affect either angiotensin induced presser or antina triuretic responses. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly di fferent from control in both groups of rats. These data confirm that l ow dose ICV AII causes hypertension and sodium retention in rats raise d from early age on moderately elevated sodium intakes. This AII media ted neurogenic hypertension and antinatriuresis is transduced by activ ation of CNS AT, receptors and not by activation of central AT, recept ors. (C) 1998 Published by Elsevier Science B.V. All rights reserved.