ANTAGONISM BY IDAZOXAN AT LOW-DOSE BUT NOT HIGH-DOSE, OF THE NATRIURETIC ACTION OF MOXONIDINE

Citation
Dr. Allan et al., ANTAGONISM BY IDAZOXAN AT LOW-DOSE BUT NOT HIGH-DOSE, OF THE NATRIURETIC ACTION OF MOXONIDINE, British Journal of Pharmacology, 117(1), 1996, pp. 29-34
Citations number
29
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
00071188
Volume
117
Issue
1
Year of publication
1996
Pages
29 - 34
Database
ISI
SICI code
0007-1188(1996)117:1<29:ABIALB>2.0.ZU;2-K
Abstract
1 Recent studies concerning the imidazoline receptor have utilized ida zoxan as a specific imidazoline receptor antagonist. The aim of the pr esent study was to describe the in vivo effects of various doses of id azoxan on renal function, in the presence and absence of moxonidine, a n I-1 imidazoline receptor agonist. 2 In anaesthetized, unilaterally n ephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusi on of moxonidine (3 nmol kg(-1) min(-1)) increased urine flow rate, so dium excretion and osmolar clearance without altering free water clear ance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg(-1) produced a dose-related decrease in the renal actions of moxonidine. H owever, a higher dose of idazoxan (1 mg kg(-1)) was not as effective a s 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 uri ne flow rate and sodium excretion. However, idazoxan at 1 mg kg(-1) pr oduced 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 antagonizin g the sites stimulated by moxonidine (renal imidazoline receptors). Ho wever, at higher doses, idazoxan may function as a partial agonist and /or interact with other receptors to increase urine how rate, independ ent of imidazoline receptor blockade. These studies underscore the imp ortance of the dose of idazoxan administered when this antagonist is u sed as a tool to investigate imidazoline receptors.