Mineralocorticoid and angiotensin receptor antagonism during hyperaldosteronemia

Anastasia S. Mihailidou*, Mahidi Mardini, John W. Funder, Matthew Raison

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Elevated aldosterone levels induce a spironolactone-inhibitable decrease in cardiac sarcolemmal Na+-K+ pump function. Because pump inhibition has been shown to contribute to myocyte hypertrophy, restoration of Na+-K+ pump function may represent a possible mechanism for the cardioprotective action of mineralocorticoid receptor (MR) blockade. The present study examines whether treatment with the angiotensin type 1 receptor antagonist losartan, with either spironolactone or eplerenone, has additive effects on sarcolemmal Na+-K+ pump activity in hyperaldosteronemia. New Zealand White rabbits were divided into 7 different groups: controls, aldosterone alone, aldosterone plus spironolactone, aldosterone plus eplerenone, aldosterone plus losartan, aldosterone plus losartan and spironolactone, and aldosterone plus losartan and eplerenone. After 7 days, myocytes were isolated by enzymatic digestion. Electrogenic Na+-K+ pump current (Ip), arising from the 3:2 Na+:K+ exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered Ip; treatment with losartan reversed aldosterone -induced reduced pump function, as did MR blockade. Coadministration of spironolactone or eplerenone with losartan enhanced the losartan effect on pump function to a level similar to that measured in rabbits given losartan alone in the absence of hyperaldosteronemia. In conclusion, hyperaldosteronemia induces a decrease in Ip at near physiological levels of intracellular Na+ concentration. Treatment with losartan reverses this aldosterone-induced decrease in pump function, and coadministration with MR antagonists produces an additive effect on pump function, consistent with a beneficial effect of MR blockade in patients with hypertension and congestive heart failure treated with angiotensin type 1 receptor antagonists.

Original languageEnglish
Pages (from-to)124-129
Number of pages6
JournalHypertension
Volume40
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Aldosterone
  • Hypertrophy
  • Ion transport
  • Myocytes
  • Rabbits
  • Sodium-potassium pump

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