Renal imidazoline preferring sites and solute excretion in the rat.
1. Moxonidine has been found to have an approximately 600 fold greater affinity for I1 imidazoline preferring sites as compared to alpha 2-adrenoceptors in the rat kidney. The effects of an intrarenal infusion of moxonidine in an anaesthetized rat preparation were investigated and contrasted with the effects previously reported for alpha 2-adrenoceptor stimulation. 2. An intrarenal infusion of moxonidine (1, 3 and 10 nmol kg-1 min-1) produced an increase in urine flow rate and sodium excretion. Moxonidine increased urine volume through an increase in osmolar clearance rather than an increase in free water clearance as previously reported for alpha 2-adrenoceptor stimulation. 3. The effects of moxonidine also appeared to be unique from the effects of alpha 2-adrenoceptor stimulation. An imidazoline preferring site specific blocking dose of idazoxan (0.3 mg kg-1), but not an alpha 2-adrenoceptor specific blocking dose of rauwolscine (0.3 mg kg-1) attenuated the renal effects of moxonidine (3 nmol kg-1 min-1). Moreover, unlike alpha 2-adrenoceptor agonists, the effects of moxonidine were not altered by prior treatment with a V2 vasopressin receptor antagonist. 4. These results indicate differences between stimulation of alpha 2-adrenoceptors and I1 imidazoline preferring sites in the rat kidney and suggest a direct physiological function of renal imidazoline preferring sites.
Allan
D R
DR
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Penner
S B
SB
Smyth
D D
DD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism* / Q000494:pharmacology; D054755:Imidazoline Receptors; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D017483:Receptors, Vasopressin; D003404:Creatinine; C043482:moxonidine