AT1 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 relatively high sodium chloride diet (250 meq kg(-1)food) from weaning. This experimental model of hypertension is dependent upon renal sympathetic innervation and associated with neurogenic sodium retention. This study determined whether AT1 and/or AT2 receptor subtypes in the CNS mediate this neurogenic ICV AII hypertension. Rats were weaned at 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 cannulas, femoral arterial and vein catheters and housed in metabolic pens for chronic study. Low dose ICV AII infusion (20 ng min(-1) )increased mean arterial pressure by 12+/-2 mm Hg and decreased urinary sodium excretion for three consecutive days. Subsequent ICV AT1 blockade with losartan abolished both the pressor and antinatriuretic responses to low dose ICV AII. In contrast, ICV AT2 receptor blockade with PD 123319 did not affect either angiotensin induced pressor or antinatriuretic responses. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly different from control in both groups of rats. These data confirm that low dose ICV AII causes hypertension and sodium retention in rats raised from early age on moderately elevated sodium intakes. This AII mediated neurogenic hypertension and antinatriuresis is transduced by activation of CNS AT1 receptors and not by activation of central AT2 receptors.
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
A K
AK
Camara
J L
JL
Osborn
D000804:Angiotensin II / Q000008:administration & dosage; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000652:urine; D002908:Chronic Disease; D004039:Diet, Sodium-Restricted; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology / Q000652:urine; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D014886:Weaning
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019808:Losartan