Dose selective dissociation of water and solute excretion after renal alpha-2 adrenoceptor stimulation.
In vitro studies have demonstrated an antagonism of the renal effects of vasopressin after alpha-2 adrenoceptor stimulation. Whether the effect of alpha-2 adrenoceptor stimulation in relation to sodium and water excretion in vivo is mediated through independent mechanisms is unclear. The dose-response relationship between renal alpha-2 adrenoceptor stimulation (clonidine) and water and electrolyte excretion was evaluated in anesthetized rats. Rats were nephrectomized unilaterally 7 to 10 days before the experimental day to allow isolation of renal function. A base-line level of sodium and water excretion was established by the infusion of saline (0.097 ml/min i.v.). In separate groups of rats, clonidine was infused directly into the renal artery at 0 (vehicle), 0.1, 0.3, 1 or 3 micrograms/kg/min at 0.0034 ml/min. The lower doses (0.1, 0.3 and 1 microgram/kg/min) produced a dose-related increase in urine volume and free water clearance and a decrease in urine osmolality. Electrolyte or solute excretion was not altered at these infusion rates even though urine volume increased 4-fold. The highest dose investigated (3 micrograms/kg/min) increased urine volume (9-fold) and sodium excretion (4-fold). Free water clearance and osmolar clearance were also increased. The effects of clonidine were attenuated by yohimbine but not prazosin indicating these effects were mediated by alpha-2 adrenoceptor stimulation. These results demonstrate a dose-related selectivity of alpha-2 adrenoceptor stimulation for water and sodium excretion. The increase in water excretion at the lower infusion rates would be consistent with the antagonism of the renal effects of vasopressin. The potent natriuresis observed only at higher doses indicates another mechanism may be involved.
Blandford
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Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada.
Smyth
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D004573:Electrolytes; D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin