Requirements for a high rate of potassium excretion in rats consuming a low electrolyte diet

Abstract

Control mechanisms for potassium (K(+)) excretion in humans developed in Palaeolithic times when diets were sodium poor and episodically K(+) rich. Nevertheless, our understanding of the regulation of K(+) excretion comes from experiments in rats with large sodium and K(+) intakes. Our objective was to identify how K(+) excretion was regulated when rats consumed a low NaCl diet to reflect Palaeolithic conditions. Rats that were given mineralocorticoids plus either NaCl, mannitol, or NaHCO(3) had a small kaliuresis. In contrast, KCl load induced a large kaliuresis and a near-maximal luminal [K(+)] in the terminal cortical collecting duct ([K(+)](CCD)). The time course of events was important. The rise in the [K(+)](CCD) was prompt, but the initial kaliuresis was only modest. Over the next 4 h, kaliuresis increased markedly due solely to a higher calculated distal flow rate, which appeared to be due to diminished reabsorption of NaCl in the loop of Henle; of note, the measured papillary [K(+)] rose. In summary, the increase in the [K(+)](CCD) in rats given KCl is likely to be due to an increase in the number of luminal K(+) channels rather than to mechanisms that are known to induce a lumen-negative voltage in cortical distal nephron segments. The higher distal flow rate might be due to a higher interstitial [K(+)], which inhibited NaCl reabsorption in the loop of Henle. Thus, to understand which of the potential control mechanisms are operating, one must look very closely at the conditions imposed by the experimental setting.

Figure 1. Effect of DOC on the parameters for K⁺ excretion in rats consuming the low electrolyte diet

The results are given as the mean ± s.e.m. for 11 rats in each group. A, urinary flow rate (depicted by the stippled, wider rectangles) and rate of excretion of K⁺ (depicted by the open, narrower rectangles). B, flow rate in the terminal CCD (depicted by the stippled, wider rectangles) and [K⁺]_CCD (depicted by the open, narrower rectangles). There were no significant differences in these results. In A and B, dDAVP alone is shown on the left, and dDAVP plus DOC on the right.

Figure 2. Effect of NaHCO₃ or KCl on the parameters for K⁺ excretion in rats consuming the low electrolyte diet

The results are the mean ± s.e.m. for 7 rats that received NaHCO₃ and the 10 rats that received KCl. A, rate of excretion of Na⁺ (depicted by the stippled, wider rectangles) and rate of excretion of K⁺ (depicted by the open, narrower rectangles). B, flow rate in the terminal CCD (depicted by the stippled, wider rectangles) and [K⁺]_CCD (depicted by the open, narrower rectangles). In A and B, the NaHCO₃ group is shown on the left and the KCl group on the right. *P < 0.05 for the effect of an infusion of KCl.

Figure 3. Effect of an infusion of mannitol on the rate of excretion of K⁺ and [K⁺]_CCD in rats pretreated with DOC

The results are the mean ± s.e.m. for 7 rats in each group. The urine flow rate is shown on the x-axis; the two higher flow rates were caused by an infusion of mannitol (see Methods for details). ▪, rate of excretion of K⁺; this rate was not significantly different at the different urine flow rates. ○, [K⁺]_CCD; this latter concentration was significantly lower at the highest urine flow rate. *P < 0.05 for the effect of a change in the urine flow rate.

Figure 4. Time course for K⁺ excretion parameters in rats given a KCl supplement

For details, see Methods. The time after administering KCl is shown on the x-axis. A, ○, the flow rate in the terminal CCD μl min⁻¹; ▪, rate of excretion of K⁺ in μmol min⁻¹. B, ○, the urine flow rate in μl min⁻¹; ▪, [K⁺]_CCD. Notice how closely the rate of excretion of K⁺ mirrors the urine flow rate and that the [K⁺]_CCD rises initially and does not change appreciably thereafter. *P < 0.05 for the effect of an infusion of KCl.

Figure 5. Effect of KCl administration on loop of Henle function

The results are the mean ± s.e.m. for 7 rats in the NaCl group and 10 rats in the KCl group. A, urinary flow rate (depicted by the stippled, wider rectangles) and urine osmolality (depicted by the open, narrower rectangles). B, Na⁺ plus K⁺ excretion rate (depicted by the stippled, wider rectangles) and papillary [K⁺] (depicted by the open, narrower rectangles). In A and B, the NaCl supplement group is shown on the left and the KCl supplement group on the right. *P < 0.05 for the effect of an infusion of KCl.