Renal imidazoline preferring sites and solute excretion in the rat

• Published in: British journal of pharmacology Vol. 108; no. 4; pp. 870 - 875
• Main Authors: Allan, D.R., Penner, S.B., Smyth, D.D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-1993; Nature Publishing
• Subjects: Adrenergic alpha-Agonists - pharmacology; Anesthesia; Animals; Antidiuretic Hormone Receptor Antagonists; Antihypertensive Agents - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; clonidine; Creatinine - metabolism; Imidazoles - metabolism; Imidazoles - pharmacology; Imidazoline Receptors; Kidney - metabolism; Male; Medical sciences; Miscellaneous; Moxonidine; natriuresis; Natriuresis - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptors, Drug - drug effects; Receptors, Drug - metabolism; Receptors, Vasopressin - metabolism; Urodynamics - drug effects; vasopressin (V2) antagonist; α2‐adrenoceptor; α2-Adrenergic receptor; Agonist; Pathophysiology; Rat; Rodentia; Natriuria; Biological activity; Kidney; Vertebrata; Biological fixation; Mammalia; Animal; Antihypertensive agent; Mechanism of action; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13480.x

1
Moxonidine has been found to have an approximately 600 fold greater affinity for I1 imidazoline preferring sites as compared to α2‐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 α2‐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 α2‐adrenoceptor stimulation.
3
The effects of moxonidine also appeared to be unique from the effects of α2‐adrenoceptor stimulation. An imidazoline preferring site specific blocking dose of idazoxan (0.3 mg kg−1), but not an α2‐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 α2‐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 α2‐adrenoceptors and I1 imidazoline preferring sites in the rat kidney and suggest a direct physiological function of renal imidazoline preferring sites.