K+ deprivation potentiates the renal acid excretory effect of mineralocorticoid: obliteration by amiloride

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Abstract
In dogs preexisting dietary K+ restriction exaggerates the acid excretory response to pharmacological doses of mineralocorticoid hormone (MCH) and thereby potentiates the alkalosis-producing effect of the hormone. The exaggerated increase in net acid excretion (NAE) was the combined result of an enhanced urine pH-lowering effect of MCH and an enhanced rate of renal ammonia production. The effect on this amplification of amiloride, a natriuretic agent known to act selectively in the distal nephron and block MCH-dependent Na+ reabsorption and lumen-negative potential difference in collecting tubules was studied. Pretreatment with amiloride completely blocked the amplified portion of the acid excretory response to MCH conditioned by preexisting K+ restriction (LO K+), but did not prevent the occurrence of a response equivalent to that observed in K+-replete (NL K+) control dogs. Amplification of the acid excretory response to MCH in LO K+ dogs is mediated in an amiloride-sensitive segment(s) of the distal nephron and excludes a major contribution to the amplification phenomenon by the enhanced proximal tubular bicarbonate reabsorptive capacity known to result from K+ depletion. Similar inhibition of the amplification phenomenon was observed when amiloride administration followed pretreatment with MCH in LO K+ and NL K+ dogs. The amplification phenomenon conditioned by LO K+ may be mediated by an accentuated increase in MCH-dependent transtubular potential difference.