The Malvin, Sullivan and Wilde ( The Physiologist 1: 58, 1957) stop flow technique for the localization of tubular function has been applied to a study of potassium and acid excretion in the dog. It has been observed that the urine is acidified in the distal part of the nephron at a site of avid sodium reabsorption. Potassium and ammonia are secreted in the same portion of the tubule. Diamox reduces acidification of the urine and secretion of ammonia and enhances the secretion of potassium. Phosphate is reabsorbed in the proximal part of the nephron in a region which is coextensive with that which secretes p-aminohippurate. All our data are consonant with the view that a mechanism located in the distal part of the nephron exchanges cellular hydrogen and/or potassium ions for sodium ions in the tubular urine. Ammonia diffuses into acid urine and is trapped as ammonium ion. Diamox, by interfering with the supply of cellular hydrogen ions, reduces exchange of hydrogen for sodium and favors the exchange of potassium for sodium.
Infusion of magnesium chloride markedly increased the excretion of calcium in dogs. A slight but significant increase in the excretion of magnesium occurred following the infusion of calcium chloride. Utilizing the stop-flow technique it was noted that magnesium and calcium achieved minimal concentration ratios in the distal segments of the nephron. Infusion of magnesium chloride during stop-flow studies increased U/PCa/U/PCr ratios both in the proximal and distal samples. These observations support the postulate that magnesium and calcium compete for a common reabsorptive system in the renal tubules. In several stop-flow experiments Mg28 and Ca45 were injected along with inulin 1 or 2 minutes before releasing the ureteral occlusion. Mg28 and Ca45 appeared simultaneously in the urine prior to the appearance of inulin, suggesting transtubular flux of these cations. Such observations, while indicating bidirectional movement of these ions across the tubular epithelium, do not imply active or net secretion.
Effects on sodium reabsorption and oxygen consumption of the renal arterial injection of three metabolic inhibitors were studied by unilateral clearance techniques in anesthetized dogs. In control studies, 21.5 ± 2.3 mEq sodium were reabsorbed per millimole oxygen consumed within a range of sodium reabsorption of from 2 to 9 mEq/min. A total dose of 10–4 m cyanide depressed both sodium reabsorption and oxygen consumption in the injected kidney. Administration of 10–4 m Q0, the quinone nucleus of coenzyme Q, reduced sodium reabsorption and had a variable effect on O2 consumption. Dinitrophenol, in a total dose of 10–3 m, increased oxygen consumption without affecting the per cent of filtered sodium that was reabsorbed. The resultant Na:O2 ratios were 12:1. We conclude that the major fraction of O2 consumption energizes sodium reabsorption in the kidney perhaps via the classic route of ATP synthesis and hydrolysis. However, all three compounds used in this study would be predicted to decrease renal ATP concentrations. Yet only cyanide and Q0 decreased sodium reabsorption. Energy for sodium movement may come directly from oxidative metabolism bypassing synthesis and breakdown of ATP.
Localization of urate transport within the nephrons of mongrel and Dalmatian dogs was studied by stop-flow analysis. In mongrel dogs urate concentrations and clearance ratios were lowest in the segment in which PAH was secreted. Urate clearance ratios of 0.7 in free-flow samples were reduced to about 0.3 in stop-flow samples from the proximal segment. In the distal segment urate clearance ratios did not differ significantly from ratios obtained in free-flow. Probenecid, in doses sufficient to block PAH secretion, inhibited urate reabsorption thereby increasing urate clearance. In contrast to these findings with mongrel dogs, the Dalmatians exhibited weak but definite urate secretion within the proximal segment. The action of probenecid in this strain of dogs was to stop all proximal secretory activity for urate thereby reducing urate clearance. It was suggested that mongrel and Dalmatian dogs transport urate by systems that are identical except for direction of urate movement.
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