Enhanced natriuretic potency of intravenous clonidine: extrarenal site of action?
We have previously demonstrated that low intrarenal infusion rates of clonidine selectively increased water excretion, whereas higher infusion rates were required to increase solute excretion. This is in contrast to previous experiments where intravenous administration of clonidine resulted in a concomitant increase in water and sodium excretion. We therefore determined the dose response curve for an intravenous infusion of clonidine on water and solute excretion and compared this to the effects of an intrarenal infusion. Uninephrectomized rats were anesthetized and the remaining kidney isolated for the collection of urine. Clonidine (0.1, 0.3, 1 or 3 micrograms/kg per min) or vehicle (saline) was administered either intravenously or intrarenally. Both intravenous and intrarenal administration of clonidine produced a dose selective dissociation of water and solute excretion, that is, at low infusion rates only urine volume was increased. Higher infusion rates were required to increase sodium excretion. In addition, intravenous administration of clonidine was more potent in producing a natriuresis, suggesting that the renal effects may be, in part, secondary to additional peripheral and/or central effects of this agonist following this route of administration.
Blandford
D E
DE
Department of Pharmacology, University of Manitoba, Winnipeg, Canada.
Smyth
D D
DD
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009392:Nephrectomy; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D012964:Sodium; D003000:Clonidine; D011188:Potassium