ANP differentially modulates marinobufagenin-induced sodium pump inhibition in kidney and aorta

Olga V. Fedorova, Natalia I. Agalakova, Christopher H. Morrell, Edward G. Lakatta, Alexei Y. Bagrov

Research output: Contribution to journalArticle

Abstract

NaCl loading and plasma volume expansion stimulate 2 natriuretic systems, vasoconstrictor, digitalis-like Na/K-ATPase inhibitors and vasorelaxant ANP peptides. Several hormones, including ANP, regulate activity of the Na/K-ATPase by modulation of its phosphorylation state. We studied effects of ANP on Na/K-ATPase phosphorylation and inhibition by an endogenous sodium pump ligand, marinobufagenin, in the aorta and renal medulla from male Sprague-Dawley rats. Marinobufagenin dose-dependently inhibited the Na/K-ATPase in renal and vascular membranes at the level of higher (nanomolar) and lower affinity (micromolar) binding sites. Marinobufagenin (1 nmol/L) inhibited Na/K-ATPase in aortic sarcolemma (18%) and in renal medulla (19%). prepro-ANP 104 to 123 (ppANP) and α-human ANP ([α-hANP] both 1 nmol/L) potentiated marinobufagenin-induced Na/K-ATPase inhibition in the kidney, but reversed the effect of marinobufagenin in the aorta. Similarly, ppANP and α-hANP modulated the sodium pump (ouabain-sensitive Rb uptake) inhibitory effects of marinobufagenin in the aorta and renal medulla. In renal medulla, ppANP and α-hANP induced α-1 Na/K-ATPase phosphorylation, whereas in aorta, both peptides dephosphorylated Na/K-ATPase. The effect of ppANP on Na/K-ATPase phosphorylation and inhibition was mimicked by a protein kinase G activator, 8-Br-PET-cGMP (10 μmol/L), and prevented by a protein kinase G inhibitor, KT5823 (60 nmol/L). Our results suggest that α-1 Na/K-ATPase inhibition by marinobufagenin in the kidney is enhanced via Na/K-ATPase phosphorylation by ANP, whereas in the aorta, ANP exerts an opposite effect. The concurrent production of a vasorelaxant, ANP, and a vasoconstrictor, marinobufagenin, potentiate each other's natriuretic effects, but ANP peptides may offset the deleterious vasoconstrictor effect of marinobufagenin.

Original languageEnglish (US)
Pages (from-to)1160-1168
Number of pages9
JournalHypertension
Volume48
Issue number6
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • ANP
  • Marinobufagenin
  • Natriuretic hormones
  • Ouabain
  • Sodium-potassium exchanging adenosinetriphosphatase
  • cGMP

ASJC Scopus subject areas

  • Internal Medicine

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