Response to mercurial diuretics during alkalosis: a comparison of acute metabolic and chronic hypokalemic alkalosis in the dog.

A relationship between the action of mercurial diuretics and acid-base metabolism has been established for many years. Diuresis may be augmented by the administration of acidifying salts such as ammonium chloride (1), and may be decreased or even totally inhibited by alkalinizing agents (2, 3). Although a variety of clinical and experimental studies suggest that the mercurials act by decreasing the tubular reabsorption of the chloride ion (37), it is not clear exactly why this action of the drug is so susceptible to changes in acid-base balance. Recent reviews have emphasized the role of glomerular factors in determining the response to mercurials. Potentiation by ammonium chloride has been attributed to an increase in the filtered chloride load, rather than to changes in the pH of the serum or of the urine (3). Conversely, it has been proposed that the refractoriness seen in metabolic alkalosis is due to a decrease in the amount of chloride filtered at the glomerulus (7). In addition, when the level of serum chloride is kept constant but the filtration rate is changed, the diuretic effect of the mercurials varies directly with the filtered chloride load (8). It had previously been postulated that the pH of the tubular urine, or of the surrounding cells, might directly modify the dissociation of the mercurial and hence determine the extent to which mercury became affixed to the tubule (9). Although changes in the reactivity of the tubule to mercury have not been directly demonstrated, this possibility continues to be suggested by several observations which can not be explained solely