The paradoxical effect of adrenomedullin on Na+ transport by the renal distal tubule luminal membrane.

Adrenomedullin (ADM) is a potent hypotensive and natriuretic peptide which is synthetized in several mammalian tissues including the kidney. The purpose of this study was to investigate whether the natriuresis was due to a change in Na+ transport by either the proximal (PT) or the distal tubule (DT) luminal membrane, and to characterize this effect, if present. PT and DT suspensions were incubated with human ADM for 20 min at 37 degrees C and luminal membranes of these tubules were purified using the Mg2+ precipitation technique. Na+ uptake was measured by the Millipore filtration technique. A volume of 10(-8) M ADM had no effect on Na+ uptake by the PT luminal membranes. In contrast and unexpectedly, the hormone increased Na+ transport by the DT membranes from 0.28 +/- 0.03 to 0.68 +/- 0.06 pmol/microg per 5 s (P < 0.01). The dose-response curve of this effect showed a maximal response with 10(-7) M ADM. The hormone influenced exclusively the Na+/H+ exchanger, leaving the N-ethyl-N-isopropyl-amiloride (EIPA) insensitive transport intact. The addition of Rp cAMPs to the preparations completely abolished the effect of the hormone on Na+ transport suggesting that cAMP was the messenger involved in this action. Finally, incubation of the DT suspensions with aldosterone also stimulated 1 mM Na+ uptake by the luminal membrane and the two hormone actions were not additive. We conclude that, although ADM is a natriuretic hormone probably through its vasodilating action, it increases distal Na+ reabsorption by the stimulation of the Na+/H+ exchanger activity, as does aldosterone at the same site.