Stereospecificity of the effects of ozolinone on renal hemodynamics and on segmental tubular sodium reabsorption in conscious rats.
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.
Shalmi
M
M
Department of Pharmacology, University of Copenhagen, Denmark.
Petersen
J S
JS
Christensen
S
S
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*
D004232:Diuretics; D013844:Thiazoles; C018121:ozolinone; D008094:Lithium; D012964:Sodium