Renal ammoniagenic factor in the plasma of rats with acute metabolic acidosis

The acute metabolic responses to metabolic acidosis in the rat include an increase in ammoniagenesis and gluconeogenesis before enzyme adaptations have taken place. In the present studies rats were made acidotic with NH₄Cl or HCl. Preincubation of renal cortical slices from normal rats in plasma from acidotic rats produced an increase in ammoniagenic capacity. However, when slices were incubated directly in diluted plasma from acidotic rats, there was also an increase in ammoniagenesis and gluconeogenesis from glutamine. The ammoniagenic factor was detectable within 0.5 hr of induction of acidosis, was not detectable in chronic acidosis, was not of adrenal origin, was not a protein, was dialyzable, and acted by an α-adrenergic-like mechanism in that its action was blocked by phentolamine but not by propranolol. Phentolamine injected into rats depressed the ammoniagenic response to acidosis. The plasma factor did not show its ammoniagenic effect in a low-sodium buffer and there was no absolute requirement for calcium. The acute response to acidosis is thus mediated by a humoral substance with the above characteristics.