, Volume 304, Issue 3, pp 289-296

Effects of ozolinone, a diuretic active metabolite of etozoline, on renal function

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The effects of ozolinone (3-methyl-4-oxo-5-piperidino-thiazolidine-2-ylidene) on renal tubular and glomerular functions were studied in rats using clearance and micropuncture techniques. Ozolinone (50 mg·kg−1 i.v., 50 mg·kg−1·h−1i.v.) markedly increased urine volume, urinary sodium excreation and — to a minor extent — also urinary potassium excretion. Fractional tubular sodium reabsorption fell by 14%. Renal blood flow, as measured by an electromagnetic flowmeter, increased considerably during the administration of the drug. Despite the fact that ozolinone increased intratubular hydrostatic pressure, whole kidney as well as single nephron GFR—measured at different tubular sites — remained constant due to an increase in glomerular capillary pressure (stopped flow measurements, servo nulling technique). The diuretic decreased intrinsic reabsorptive capacity of the proximal tubular epithelium as measured with the shrinking drop technique of Gertz, but had no clearcut effects on proximal fractional reabsorption. Fractional reabsorption was evaluated not only from free flow endproximal tubular fluid to plasma inulin measurements but also from transit time and half time of reabsorption (shrinking drop technique). An impressive depression of fluid, sodium and potassium reabsorption occurred in the loops of Henle after ozolinone. No further inhibition of fluid and sodium reabsorption in the distal convoluted tubules could be detected after the drug using a free flow recollection technique. Concerning the tubular site of renal action there is a striking similarity between ozolinone and the strong acting diuretic furosemide, although the chemical structures of these drugs are quite different. Differences between the two drugs exist concerning the endproximal tubular chloride concentration, which was decreased by furosemide but was not affected by ozolinone. This points to different effects of the drugs on proximal tubular bicarbonate reabsorption.