On the Mechanism of Nitrate-Induced Alkalosis. The Possible Role of Selective Chloride Depletion in Acid-Base Regulation*

Abstract

It has recently been demonstrated that the rate of both hydrogen and potassium excretion can be acutely increased when a disproportion is created between the quantity of sodium and the quantity of penetrating anion available for reabsorption (1). This experimental condition was achieved by the infusion of neutral sodium phosphate into animals which had previously been maintained on a diet poor in sodium chloride. Such short-term observations raised the possibility that sustained changes in availability of penetrating anion might of themselves induce chronic alterations in body fluid composition. This hypothesis was supported by the subsequent observation that restriction of dietary chloride prevents correction of plasma bicarbonate elevations induced by chronic hypercapnia or administration of desoxycorticosterone acetate (DOCA) (2, 3). In each of the latter circumstances, however, the elevated plasma bicarbonate presumably developed as a result of direct acceleration of sodium-cation exchange and these observations, therefore, throw no light on the possible consequences of a primary loss of chloride in a normal animal. Such a loss might be expected to produce either secondary sodium (and volume) depletion, diversion of sodium reabsorption to the cation-exchange mechanism, or some combination of the two. In order to investigate this problem, chloride deficiency has been produced in dogs by the repeated infusion of nitrate, an anion known to induce chloruresis (4).

The renal response to acid loads in metabolic alkalosis; an assessment of the mechanisms regulating acid excretion.

“…However, when administered with a reabsorbable anion such as chloride, these ions are promptly conserved (4,5,11). In the present study, when chloride was provided as hydrochloric acid, the reabsorbable anion permitted sodium and potassium present in the diet to be retained but only at the price of leaving the phosphate anions stripped of the cations with which they had entered the body.…”

“…In group IB (seven dogs) the sodium and potassium supplement was withdrawn from the diet before the administration of hydrochloric acid; in five of these dogs the electrolyte supplement was withdrawn on the same day that hydrochloric acid administration was begun, and in the remaining dogs the administration of hydrochloric acid was delayed until 7 days after the supplement had been withdrawn. (5). Since the response to nitric acid was essentially the same in dogs rendered alkalotic by either method, the data from the entire group have been pooled and will be considered together in the remainder of the paper.…”

The induction of metabolic alkalosis by correction of potassium deficiency.

“…1 The magnitude of this response is not influenced by the buffer characteristics of the administered anion, since sulfate, a nonbuffer, was just as effective as phosphate in producing the acid-base abnormalities. It is also of interest that the continued presence in the diet of potassium and the nonreabsorbable anion was not necessary for maintenance of alkalosis; withdrawal of the potassium salt led to only a slight fall in plasma bicarbonate concentration.…”

“…Recent studies in both dog and man have challenged the widely held concept that repair of potassium deficiency is a prerequisite to the correction of metabolic alkalosis; ready and sustained correction of alkalosis has been shown to follow the administration of chloride, as either sodium chloride or hydrochloric acid, even when the diet is free of potassium (1)(2)(3)(4). Furthermore, it has been shown that correction of an alkalosis by hydrochloric acid is sometimes retarded by the simultaneous repair of potassium and sodium deficiency (3).…”

The Role of Chloride in Hypokalemic Alkalosis in the Rat*

“…Schwartz and co-workers (9,21) have shown in dogs that neither plasma electrolyte changes due to potassium deficiency nor the potassium deficiency itself can be fully corrected by the administration of a potassium salt other than chloride. The daily intraperitoneal administration to potassium-deficient rats of potassium bicarbonate, 6 mmoles per kg body weight, during periods ranging from 3 to 11 days (Table IV), failed to fully correct either the potassium deficit or the hypochloremic alkalosis.…”