Mechanisms of ozolinone-induced renin release and diuresis.
Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4.0 +/- 0.3 v 0.9 +/- 0.1 mL/min (P < .001); FENa+ 29.8 +/- 3.0 v 5.6 +/- 0.3% (P < .001); FECl- 35.7 +/- 4.1 v 5.8 +/- 0.4% (P < .001); FEK+ 87 +/- 4 v 49 +/- 5% (P < .001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) did not change. The renin secretory rate (RSR) was significantly higher with (-)ozo than with (+)ozo (498 +/- 113 v 210 +/- 53 ng A I/mL/hr.mL/min). Moreover, (-)ozo significantly increased urine PG excretion compared to basal values: 466 +/- 63 v 263 +/- 30 pg/min (P < .05). Indomethacin (2 mg/kg) markedly blunted the effects of (-)ozo on PG and RSR, and completely abolished the rise in PRA. (+)Ozo had no significant effect on urine PG excretion. Neither (-)ozo nor (+)ozo had an effect on renin production in isolated glomeruli. By contrast, (-)ozo but not (+)ozo increased PGE2 synthesis in papillary and medullary slices. The data are consistent with the proposal that the effect of (-)ozo on renin secretion and PRA is through a PG-dependent mechanism, and that it requires an intact macula densa mechanism.
Benabe
J E
JE
Department of Medicine, Emory University School of Medicine, Atlanta VA Medical Center, Decatur, Georgia.
Pedraza-Chaverri
J
J
Martínez-Maldonado
M
M
D000818:Animals; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000096:biosynthesis; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000378:metabolism* / Q000652:urine; D013237:Stereoisomerism; D013844:Thiazoles / Q000494:pharmacology*
D002712:Chlorides; D004232:Diuretics; D011453:Prostaglandins; D013844:Thiazoles; C018121:ozolinone; D012083:Renin; D011188:Potassium; D007213:Indomethacin