Role of vasopressin in response to intrarenal infusions of alpha-2 adrenoceptor agonists.
Previous studies have indicated that the effects of renal alpha-2 adrenoceptor stimulation are mediated through the blockade of the renal effects of vasopressin. If this premise is correct then 1) specific antagonists of the antidiuretic effect of vasopressin (V2 antagonists) should mimic alpha-2 adrenoceptor stimulation and 2) in the presence of V2 antagonists, the diuretic and natriuretic effect of clonidine should be attenuated. The renal effects of [d(CH2)5,D-Ile2,Ile4]AVP, a specific V2 antagonist, were studied. On the day of the experiment, uninephrectomized rats were anesthetized, and the carotid artery and jugular vein were cannulated for recording blood pressure and saline infusion, respectively. The left kidney was exposed and the ureter cannulated. A 31-gauge needle was advanced into the renal artery to permit direct i.r. infusion of study drugs. Bolus doses of the V2 antagonist (0, 1, 3, 10, or 30 nmol/kg i.v.) produced a dose-related increase in urine volume and free water clearance at all doses tested. Sodium excretion increased only at the higher doses (10 and 30 nmol/kg). This dose-related dissociation in water and then sodium excretion is similar to that observed after i.r. clonidine infusions. In the presence of the V2 antagonist, clonidine (3 micrograms/kg/min) had no effect on urine volume or free water clearance but significantly decreased the excretion of sodium from control. These results demonstrate that V2 antagonists mimic the effects of i.r. clonidine. As well, in the absence of vasopressin (V2 antagonism), the effects of clonidine are attenuated. Moreover, they are also consistent with not only an antidiuretic role for endogenous vasopressin but also an antinatriuretic one.
Blandford
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Department of Pharmacology, University of Manitoba, Winnipeg, Canada.
Smyth
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D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D001127:Arginine Vasopressin; D012964:Sodium; D003000:Clonidine