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
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.