The Pattern of Inhibition of Proximal Tubular Reabsorption by Diuretics
The mode of action of hydrochlorothiazide, furosemide and acetazolamide was studied in the proximal convoluted tubule of rat kidney by three different micropuncture techniques. The pattern of action of these diuretics was shown to be quantitatively different, but qualitatively similar. Following the administration of these diuretics bicarbonate re-absorption decreased under free flow conditions and the sodium and bicarbonate concentration difference between blood and tubular fluid was reduced during stationary microperfusion with acetazolamide, furosemide and hydrochlorothiazide in decreasing order of effectiveness. Furthermore, following the simultaneous adnainistration of furosemide and acetalozamide an additive effect on the intrinsic reabsorptive capacity of the proximal tubule could not be demonstrated.
Our results can best be explained in terms of inhibition of sodium bicarbonate reabsorption via H+-ion secretion as first postulated by Pitts and Alexander (11); a mechanism that may be the common pathway in the mode of action of these diuretics in the proximal convoluted tubule of rat kidney.
The analysis of renal action of diuretics is concerned mainly with two questions, namely with the localization within the tubule and the cellular mode of action of these substances. Diuretic action has been demonstrated in both the proximal (1, 2, 3, 7, 9, 12) and distal (7, 9) convoluted tubules accessible to micropuncture. The analysis of the mode of action of diuretics, however, is much more difficult, since underlying cellular and biochemical mechanisms of active transport have not yet fully been clarified. Based on experimentally observed transport phenomena certain models of active transport mechanisms have been worked out. At present, therefore, it is to be shown whether drug induced changes of certain transport characteristics are in correspondence with such models of active transport or not.
KeywordsProximal Tubule Steady State Concentration Tubular Epithelium Proximal Convoluted Tubule Diuretic Action
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