Mechanism for the phosphaturia of NH4Cl: dependence on acidemia but not on diet PO4 or PTH.
The effects of metabolic acidosis on renal PO4 handling are controversial. Clearance experiments, therefore, were performed in fasted parathyroidectomized rats 1) to test the thesis that NH4Cl per se alters PO4 reabsorption, 2) to characterize the mechanisms responsible for these changes, and 3) to define the interaction of NH4Cl with parathyroid hormone (PTH) in PO4 deprivation. NH4Cl increased the clearance and fractional excretion of PO4 (FEPO4) without altering plasma PO4. Lactic acid and HCl, but not saline loading. NH4HCO3, or glutamine, produced similar effects. At steady-state phosphaturic effects of NH4Cl, neutralization of the acidemia by NaHCO3 abolished the increment. PTH (3.3 U.kg-1.h-1), superimposed on the maximal effective dose of NH4Cl (5.7 mmol.kg-1.h-1), further augmented FEPO4 (from 24.3 to 46.9%). The effects of NH4Cl (delta FEPO4 = 23 vs. 21%) and the synergism with PTH were not affected by PO4 deprivation. In both PO4 repletion and deprivation, NH4Cl increased basal and PTH-stimulated cAMP excretion, but the changes were poorly correlated with FEPO4. We conclude that NH4Cl inhibits PO4 reabsorption independent of PTH, extracellular fluid volume, natriuresis, NH4+ ion, plasma PO4, or the status of PO4 balance. The effects are mediated by mechanisms dependent on acidemia but are quite distinct from those of PTH. Our findings on cAMP are most compatible with the hypothesis that biochemical events beyond cAMP generation mediate both the phosphaturia of NH4Cl and its ability to restore PTH sensitivity in PO4 deprivation.
D000641:Ammonia / Q000652:urine; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001769:Blood; D000242:Cyclic AMP / Q000652:urine; D004032:Diet; D005110:Extracellular Space / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009318:Natriuresis; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology; D010710:Phosphates / Q000502:physiology / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D010281:Parathyroid Hormone; D010710:Phosphates; D000643:Ammonium Chloride; D012965:Sodium Chloride; D000641:Ammonia; D000242:Cyclic AMP