Maleate induced fall of glomerular filtration rate

Summary

Maleate causes an enhanced excretion of amino acids, glucose, phosphate and bicarbonate. In addition to this inhibition of fluid and electrolyte reabsorption malate decreases glomerular filtration rate (GFR). The present investigation was designed to study the mechanisms of this fall in GFR.

In group I (Sprague-Dawley rats;N=8) maleate (2 mmol/kg body weight i.v.) increased the hydrostatic pressure in proximal tubule from 12.6±0.5 to 16.3±0.8 mm Hg (mean+SEM) and stop flow pressure in the first accessible loop of the proximal tubule was unchanged (33.6±0.4 vs 33.1±1.3 mm Hg; n.s.). Directly measured hydrostatic pressure in the glomerular capillaries in Munich-Wistar rats (N=7), however, was reduced by maleate from 47.6±1.6 to 42.4±1.9 mm Hg. In group II (N=8) we determined single nephron filtration rate (SNGFR) from distal and proximal collection sites in the same nephron in a paired fashion under control conditions and after maleate administration to assess the activity of the tubuloglomerular feedback. In the control periods SNGFR (16 nephrons) from distal collection sites was 26.3±1.6 nl/min whereas SNGFR from proximal collection sites was 31.8±2.4 nl/min. Following maleate distal SNGFR (17 nephrons) was 15.2±1.7 nl/min and proximal SNGFR was 24.3±2.2 nl/min. The ratio distal/proximal SNGFR was 1.23±0.07 under control conditions and increased to 1.76±0.1 following maleate indicating enhanced activity of tubuloglomerular feedback.

Following maleate (group III;N=8) the chloride concentration in the late proximal tubular fluid fell from 135±4 mmol/l to 121±6 mmol/l (13 tubules), however, in the early distal tubule we found an increase in chloride concentration from 43±3 mmol/l to 62±6 mmol/l (12 tubules). Delivery of chloride to the loop of Henle was 2,107±221 pmol/min in the control periods and decreased to 1,475±200 pmol/min during maleate. Since early distal chloride delivery increased from 199±24 pmol/min to 364±47 pmol/min following maleate inhibition of chloride reabsorption in the loop of Henle has to be assumed. We conclude that maleate decreases glomerular filtration rate first by an elevation of hydrostatic pressure in the proximal tubule which is the result of inhibition of fluid and electrolyte reabsorption, and second by activation of the tubuloglomerular feedback.