Diuretic-induced growth failure in rats and its reversal by sodium repletion

Abstract

The aim of diuretic therapy is the prevention of excessive sodium accumulation. However, sodium retention is necessary for growth. Inasmuch as many of the clinical conditions for which diuretics are used are associated with growth retardation, we investigated the influence of diuretic therapy on growth in an animal model. In Part I, 32 weanling Sprague-Dawley rats were fed a diet adequate for growth which contained 0.08% sodium and 0.17% potassium. Daily i.p. injections of saline (0.4 ml) containing furosemide in doses of 0, 50, 100 or 200 mg/M2 were given for 9 days. There was a dose-related reduction in weight gain which could not be explained by lower food intake. The highest dose group gained only 58% as much as the control group. Balance studies and muscle, bone and carcass analysis demonstrated that this was accounted for by decreases in protoplasmic, bone, fat and extracellular fluid volume accretion. In Part II, 32 weanling rats, all treated daily with furosemide (100 mg/M2 i.p.) received replacement of NaCl, KCl, both or neither in their drinking water. Sodium replacement resulted in increased growth rates whereas potassium replacement alone had no effect on growth. Sodium replacement also increased the balance of all measured minerals. We conclude that diuretic therapy causes growth retardation by preventing retention of sodium needed for growth.