Mineralocorticoid-stimulated renal acidification: the critical role of dietary sodium.
Recent in vitro studies of isolated distal nephron segments have demonstrated that mineralocorticoid hormone stimulates H+ secretion by both Na+-dependent and Na+-independent mechanisms, and the Na+-independent acidification mechanism has a greater capacity. These in vitro data suggest that mineralocorticoid administration in vivo might increase renal acid excretion when an augmentation in distal Na+ reabsorption is precluded by rigid restriction of dietary Na+; under these circumstances, virtually all Na+ delivered to the distal nephron is reabsorbed in the basal state. In the present studies, prolonged (12 days) administration of DOC (15 mg/day) was undertaken in both Na+-fed and rigidly Na+-restricted dogs with chronic HCl acidosis. Na+-fed animals responded to DOC administration with a large increment in net acid excretion and complete correction of metabolic acidosis. Marked hypokalemia and significant kaliuresis also occurred. Na+-restricted dogs experienced no changes in renal acid excretion, systemic acid-base equilibrium, plasma [K+] or K+ balance. These results suggest that both renal H+ and K+ excretory responses to prolonged mineralocorticoid hormone administration in vivo are critically dependent on the availability for reabsorption of surplus Na+ within the distal nephron; this requirement is met when the diet, and hence the final urine, contains Na+ but cannot be satisfied when dietary Na+ is rigidly restricted.
D000138:Acidosis / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D003900:Desoxycorticosterone / Q000494:pharmacology; D004032:Diet; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008901:Mineralocorticoids / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012964:Sodium / Q000494:pharmacology*
D001639:Bicarbonates; D008901:Mineralocorticoids; D011522:Protons; D003900:Desoxycorticosterone; D000641:Ammonia; D012964:Sodium; D011188:Potassium