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Maleate induced fall of glomerular filtration rate. A micropuncture study in the rat
Abstract:
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Maleate reduces glomerular filtration rate (GFR) by increasing proximal tubule pressure and enhancing tubuloglomerular feedback activity. This study investigates the mechanisms behind maleate-induced GFR reduction in rats.
Area of Science:
- Nephrology
- Renal Physiology
- Pharmacology
Background:
- Maleate administration is known to induce enhanced excretion of amino acids, glucose, phosphate, and bicarbonate.
- Maleate also inhibits fluid and electrolyte reabsorption, leading to a decrease in glomerular filtration rate (GFR).
Purpose of the Study:
- To investigate the mechanisms underlying the maleate-induced fall in glomerular filtration rate (GFR).
- To assess the impact of maleate on intra-renal pressures and tubuloglomerular feedback (TGF) activity.
Main Methods:
- Experiments were conducted on Sprague-Dawley and Munich-Wistar rats.
- Hydrostatic pressure in the proximal tubule and glomerular capillaries was measured.
- Single nephron filtration rate (SNGFR) was determined from both proximal and distal collection sites to evaluate TGF activity.
Main Results:
- Maleate increased proximal tubule hydrostatic pressure and decreased glomerular capillary hydrostatic pressure.
- The ratio of distal to proximal SNGFR increased significantly after maleate administration, indicating enhanced tubuloglomerular feedback.
- Maleate administration led to a reduction in both proximal and distal SNGFR.
Conclusions:
- Maleate reduces GFR through increased intra-renal pressures and heightened tubuloglomerular feedback activity.
- The findings elucidate the physiological mechanisms by which maleate impairs renal function.