title: Stereospecificity of the effects of ozolinone on renal hemodynamics and on segmental tubular sodium reabsorption in conscious rats.
abstract: The study was performed to elucidate the effects of the two stereoisomers of ozolinone (d,l) on renal hemodynamics and proximal tubular Na reabsorption. Clearance experiments were performed in conscious water-loaded female Wistar rats. The clearances of [3H]inulin, [14C]tetraethylammonium and lithium were used as estimates for glomerular filtration rate, renal plasma flow and delivery of fluid from the proximal tubules, respectively. When the baseline parameters had stabilized, d- or l-ozolinone was injected i.v. in doses of 4, 20 and 100 mg/kg. 1-Ozolinone caused a transient and dose-dependent diuretic-natriuretic response with no evidence of a ceiling. At peak natriuresis, 2.5-5 min after 100 mg/kg of 1-ozolinone, the fractional Na excretion was increased from 0.5 to 25%; this was associated with an increased fractional excretion of lithium from 27 to 60%, and small transient decreases of renal hemodynamic parameters. d-Ozolinone had no significant effects except for a small natriuresis after 100 mg/kg. It is concluded that in water-loaded conscious rats 1-ozolinone is a powerful diuretic which, in contrast to d-ozolinone, increases the delivery of fluid from the proximal tubule as judged from changes in lithium clearance.
authors.affiliation: Department of Pharmacology, University of Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Shalmi
authors.forename: J S
authors.initials: JS
authors.lastname: Petersen
authors.forename: S
authors.initials: S
authors.lastname: Christensen
mesh_terms: D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D013237:Stereoisomerism; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D004232:Diuretics; D013844:Thiazoles; C018121:ozolinone; D008094:Lithium; D012964:Sodium