Natriuresis following central and peripheral administration of agmatine in the rat.
Agonists specific for the I1 imidazoline receptor increase sodium excretion following intrarenal (ir) infusion or intracerebroventricular (icv) injection in the rat. Although agmatine has been suggested to be a putative endogenous agonist for these receptors, the ability of this compound to alter sodium excretion has not been determined. The effects of agmatine, whether administered ir or icv, on blood pressure and solute and water excretion were studied in Sprague-Dawley rats. Agmatine was administered by icv injection (0, 10, 100, 300 or 1,000 nmol in 5 microliters) or by direct ir infusion (0, 3, 10, 30 or 100 nmol/kg/min at 3.4 microliters/min) in pentobarbitone-anesthetized rats. Agmatine administered by icv injection or ir infusion did not alter blood pressure or heart rate. Only an ir infusion of agmatine produced an increase in creatinine clearance, which occurred at the lowest (3 nmol/kg/min) and highest dose (100 nmol/kg/min). Concomitantly, the ir infusion of agmatine produced a dose-related increase in urine flow rate, but both routes of administration were associated with an increase in sodium excretion and osmolar clearance. Similar to previous reports with I1 imidazoline receptor-selective compounds, agmatine increased urine flow rate secondary to an increase in osmolar clearance at doses that failed to alter blood pressure. These results were consistent with agmatine functioning as a physiological agonist resulting in alterations in sodium excretion.
Penner
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SB
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Smyth
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DD
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism*; D054755:Imidazoline Receptors; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists*; D014563:Urodynamics / Q000187:drug effects
D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D000376:Agmatine; D003404:Creatinine