title: Renal and systemic acid-base effects of chronic spironolactone administration.
abstract: Studies in dogs were carried out to investigate the effects of chronic administration of the mineralcorticoid antagonist spironolactone (15 mg/kg orally) on renal and systemic acid-base metabolism. In adrenalectomized dogs administered fixed mineralocorticoid and glucocorticoid replacement, spironolactone resulted in a definite renal antimineralocorticoid effect, as evidenced by natriuresis and chloruresis, and sustained metabolic acidosis and hyperkalemia due in part to impaired renal secretion of hydrogen and potassium. In adrenalectomized dogs receiving physiological glucocorticoid without mineralocorticoid, metabolic acidosis also occurred, but a marked stimulatory effect of spironolactone on net acid excretion occurred in association with increased urinary SO4-2 and total nitrogen excretion. Accordingly, spironolactone results in sustained renal tubular acidosis when administered in the presence of constant physiological levels of mineralocorticoid and glucocorticoid steroids. When administered under conditions of complete lack of mineralocorticoid activity, spironolactone exerts systemic and renal acid-base effects similar to those of a glucocorticoid steroid, namely, increased protein catabolism and sulfuric acid production with resultant extrarenal metabolic acidosis associated with increased net acid excretion.
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000315:Adrenalectomy; D000818:Animals; D004285:Dogs; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008901:Mineralocorticoids / Q000172:deficiency / Q000502:physiology; D013148:Spironolactone / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D008901:Mineralocorticoids; D013148:Spironolactone