Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.
1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excretion and osmolar clearance without altering free water clearance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg-1 produced a dose-related decrease in the renal actions of moxonidine. However, a higher dose of idazoxan (1 mg kg-1) was not as effective as the 0.3 mg kg-1 dose in blocking the effects of moxonidine. 3. In a separate series of experiments, the direct renal actions of idazoxan alone were investigated. Idazoxan at 0.3 mg kg-1 failed to alter urine flow rate and sodium excretion. However, idazoxan at 1 mg kg-1 produced a significant increase in urine flow rate and sodium excretion in association with an increase in osmolar clearance. 4. These results do not prove but are consistent with low doses of idazoxan antagonizing the sites stimulated by moxonidine (renal imidazoline receptors). However, at higher doses, idazoxan may function as a partial agonist and/or interact with other receptors to increase urine flow rate, independent of imidazoline receptor blockade. These studies underscore the importance of the dose of idazoxan administered when this antagonist is used as a tool to investigate imidazoline receptors.
Allan
D R
DR
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Penner
S B
SB
Smyth
D D
DD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000037:antagonists & inhibitors*; D054755:Imidazoline Receptors; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D003404:Creatinine; C043482:moxonidine; D019329:Idazoxan