Chapter 7. Diuretic Agents

Abstract

The reports of the advent of newer diuretics have diminished the clinical importance of organomercurial diuretics and few new compounds. Nevertheless, an active interest continues in the locus of action of this class of agents in the kidney nephron and the definition of the molecular events involved in the action of these substances on nephron function, particularly as it relates to sodium transport, potassium excretion, and effects on uric acid and glucose metabolism. Additional important evidence has been reported in support of the mercuric ion hypothesis over the intact molecule hypothesis for the action of mercurials. The mercuric ion theory implies the presence of mercuric ion in the kidney during the period of active diuresis following organomercurial administration. By using a novel isotope exchange diffusion analysis for mercury, evidence has been presented that the level of mercuric ion in the rat kidney correlated well with the onset and duration of diuresis after Hg-chlormerodrin. Mercuric ion is also released in the kidney tissue of the rabbit and chicken. Similar results are obtained in the rat with p-chloromercuribenzoic acid, an organomercurial that is not diuretic in the dog and does not release mercuric ion in a model in vitro system where other active mercurial diuretics readily yield mercuric ion. However, this substance has been shown to be rapidly diuretic in the dog when administered by retrograde infusion into the renal tubular lumen. Important studies on the locus of action in the nephron and the effect of the sodium reabsorption and oxygen consumption of these mercurials have been reported.