title: Is clonidine-induced diuresis mediated by atrial natriuretic factor?
abstract: The effect of intracerebroventricular (ICV) administration of clonidine on urine output, urinary sodium excretion, urinary cGMP, and plasma immunoreactive atrial natriuretic factor (IR-ANF) was studied in conscious, normally hydrated rats. Clonidine treatment evoked a significant dose-dependent increase in urine output. A 20-fold elevation was noted after the highest clonidine dose (2 micrograms/rat). The observed diuresis was accompanied by enhanced sodium excretion, which with the highest dose (2 micrograms) of clonidine increased from 1.6 +/- 0.36 to 39.4 +/- 10.5 meq/liter (P less than 0.001). Plasma IR-ANF rose from 30.7 +/- 8.8 to 113.3 +/- 32.3 pg/ml plasma 5 min after the 0.5 micrograms clonidine dose (P less than 0.05), and urinary cGMP excretion was augmented from 8.49 +/- 4.29 to 27.7 +/- 5.0 pmol/min 1 h after 0.5 micrograms clonidine (P less than 0.05). Pretreatment with peripherally administered anti-ANF serum abolished the diuretic effect of intracerebroventricularly administered clonidine; urine output decreased from 1.49 +/- 0.41 to 0.42 +/- 0.21 ml/h. The urinary cGMP level after anti-ANF serum treatment fell from 25.0 +/- 7.56 to 7.1 +/- 3.5 pmol/min (P less than 0.05). Peripheral pretreatment with the alpha 2-antagonist yohimbine or the opioid antagonist naloxone partially abolished clonidine's diuretic impact: urine output dropped from 1.91 +/- 0.55 to 0.42 +/- 0.18 and 0.46 +/- 0.18 ml/h (P less than 0.05), respectively. At the same time, plasma IR-ANF decreased from 113.3 +/- 32.2 to 30.3 +/- 11.4 after yohimbine and to 24.6 +/- 12.1 pg/ml after naloxone treatment (P less than 0.05). These data suggest that ANF may be involved in the mechanism of diuresis of centrally applied clonidine, which appears to enhance ANF release through its central stimulation of opiate and alpha 2-adrenergic receptors.
authors.affiliation: Clinical Research Institute of Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: J
authors.initials: J
authors.lastname: Gutkowska
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D007276:Injections, Intraventricular; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine
chemical_list: D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D003000:Clonidine