Differential effects of acute mineralo- and glucocorticosteroid administration on renal acid elimination

Differential effects of acute mineralo- and glucocorticosteroid administration on renal acid elimination. Unanesthetized, adrenalectomized rats (ADX), maintained on saline to drink and a low potassium diet, were given either vehicle alone or graded doses of aldosterone or dexamethasone (both singly and in combination) to determine the effects of mineralo- and glucocorticosteroids on renal acid excretion. Rates of phosphate excretion (U Pi V), titratable acid (U TA V) and ammonia (U amm V), and urine pH (U pH ) were measured following ammonium chloride and sodium phosphate loading. Aldosterone produced a dose-dependent fall in U pH yet increased U TA V only modestly because of a fall in U Pi V. It did not modify U amm V. Consequently, aldosterone increased net acid excretion only marginally. Dexamethasone did not alter U pH significantly. However, it increased substantially the excretion of buffer as phosphate and ammonia and, by the highest dose, more than doubled net acid excretion. The creatinine clearance of ADX rats receiving the highest dose of dexamethasone was 87% higher than those receiving the highest dose of aldosterone. The fall in blood pH and bicarbonate following ammonium chloride gavage was similar in ADX rats whether or not they were given aldosterone, yet it was significantly attenuated by dexamethasone. This indicates that the predominant effects of dexamethasone was to promote net acid excretion rather than to augment acid production. In other studies, phosphate was administered to SHAM rats and ADX rats given 20 µg/100g -1 of dexamethasone to vary urinary buffer delivery over a 100-fold range. The U TA V increased in strict proportion to U Pi V in both groups without indication of a limit to hydrogen ion secretion even in the absence of aldosterone. At comparable urinary phosphate buffer concentrations, U pH was always lower in ADX rats given aldosterone than those given dexamethasone. Thus, in the acid-loaded rat, two classes of corticosteroids have dose-dependent and discrete actions on the components of renal acid excretion. Mineralocorticosteroids promote urinary acidification whereas glucocorticosteroids promote the excretion of buffer as phosphate and ammonia. Effets differents de l'administration aigue de mineralo ou de glucocorticosteroides sur l'elimination renale des acides. Des rats eveilles surrenalectomises (ADX) buvant du solute physiologique et recevant un regime pauvre en potassium ont recu soit le vehicule seul, soit des doses croissantes d'aldosterone ou de dexamethasone (seules ou combinees) pour determiner l'effets des mineralo et des glucocorticosteroides sur l'excretion renale des acides. L'excretion urinaire des phosphates (U pi V), d'acidite titrable (U TA V) et d'ammoniaque (U amm V) et le pH urinaire (U pH ) ont ete mesures apres une surcharge en chlorure d'ammoniaque et en phosphate de sodium. L'aldosterone a entraine une chute de U pH dose-dependante mais n'a eleve U TA V que moderement en raison d'une baisse de U Pi V. Elle n'a pas modifie U amm V. L'aldosterone n'a donc augmente l'excretion acide nette que de facon marginale. La dexamethasone n'a pas modifie significativement U pH . Cependant, elle a substantiellement augmente l'excretion de tampon sous forme de phosphate et d'ammoniaque, et, a la plus forte concentration, a plus que double l'excretion acide nette. La clearance de la creatinine des rats ADX recevant la dose maximale de dexamethasone etait de 87% plus elevee que ceux recevant la dose maximale d'aldosterone. La chute du pH et des bicarbonates plasmatiques apres gavage avec du chlorure d'ammoniaque etait identique chez les rats ADX recevant ou non de l'aldosterone, mais etait significativement attenuee par la dexamethasone. Cela indique que l'effet predominant de la dexamethasone etait plus d'augmenter l'excretion acide urinaire nette que d'augmenter la production d'acides. Dans d'autres etudes, des phosphates ont ete administres a des rats controles ou a des rats ADX recevant 20 µg/100g -1 de dexamethasone afin de faire varier de 1 a 100 l'apport urinaire de tampons. U TA V s'est elevee de facon strictement proportionnelle a U Pi V dans les deux groupes sans indice d'une limite a la secretion d'ions de hydrogene, meme en l'absence d'aldosterone. Pour des concentrations identiques de tampons phosphates urinaires, U pH etait toujours plus faible chez les rats recevant de l'aldosterone que chez ceux recevant de la dexamethasone. Ainsi, chez le rat surcharge en acide, les deux classes de corticosteroides possedent des effets discrets et dose-dependants sur l'excretion acide renale. Les mineralocorticosteroides stimulent l'acidification urinaire, tandis que les glucortocitosteroides stimulent l'excretion de tampons phosphate et ammoniaque.