alpha-adrenergic systems mediate chronic central AII hypertension in rats fed high sodium chloride diet from weaning

Hypertension is elicited by chronic, low dose intracerebroventricular (ICV) angiotensin II (AII) infusion in rats raised from weaning on relatively hi gh sodium chloride diet (250 mEq kg(-1) food). This experimental model of h ypertension is dependent upon renal innervation and associated with neuroge nic sodium retention. The present study determined whether this neurogenic ICV AII hypertension is mediated by central alpha-adrenoceptors. Rats were weaned at 21 days of age and fed a 1.5% (250 mg kg(-1) food) sodium chlorid e diet for 10-12 weeks. At adulthood, animals were instrumented with centra l nervous system (CNS) lateral ventricular cannulas, femoral artery and vei n catheters and housed in metabolic pens for chronic study. Low dose ICV AI I infusion (20 ng min(-1)) increased mean arterial pressure (MAP) from 121 +/- 4 to 140 +/- 6 mm Hg on the day of ICV infusion. This increase in arter ial pressure was associated with 3 consecutive days of decreased urinary so dium excretion. Subsequent ICV alpha-adrenoceptor blockade with phentolamin e (AII + phentolamine) abolished the presser and antinatriuretic responses to low dose chronic ICV AII infusion. Resumption of ICV AII infusion alone increased in MAP toward pre-alpha-adrenergic blockade values (133 +/- 5 mm Hg) on day 8. Following cessation of ICV AII infusion, arterial pressure an d sodium excretion returned to values not significantly different from cont rol. This model of hypertension was not dependent on circulating plasma ren in activity (PRA), since PRA decreased during ICV AII infusion. These data confirm that low dose ICV AII causes hypertension and sodium retention in r ats raised from weaning on moderately elevated sodium intake. We conclude t hat AII mediated neurogenic hypertension and antinatriuresis is elicited by stimulation of AT(1) receptors on neurons which interact with noradrenergi c cell bodies in cardiovascular and autonomic centers that may modulate ren al sympathetic outflow via alpha-adrenoceptors. (C) 1999 Elsevier Science B .V. All rights reserved.