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 purpo se of this study was to investigate whether the natriuresis was due to a ch ange 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 s uspensions were incubated with human ADM for 20 min at 37 degrees C and lum inal 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 membr anes. In contrast and unexpectedly, the hormone increased Na+ transport by the DT membranes from 0.28 +/- 0.03 to 0.68 +/- 0.06 pmol/mu g per 5 s (P < 0.01). The dose-response curve of this effect showed a maximal response wi th 10(-7) M ADM. The hormone influenced exclusively the Na+/H+ exchanger, l eaving the N-ethyl-N-iso-propyl-amiloride (EIPA) insensitive transport inta ct. The addition of Rp cAMPs to the preparations completely abolished the e ffect of the hormone on Na+ transport suggesting that cAMP was the messenge r involved in this action. Finally, incubation of the DT suspensions with a ldosterone 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. (C) 2000 Elsevier Science Ireland L td. All rights reserved.