Back to Search
Start Over
Mineralocorticoid and angiotensin receptor antagonism during hyperaldosteronemia
- Source :
- Hypertension (Dallas, Tex. : 1979). 40(2)
- Publication Year :
- 2002
-
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 (I p ), arising from the 3:2 Na + :K + exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered I p ; 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 I p 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.
- Subjects :
- Male
medicine.medical_specialty
Patch-Clamp Techniques
medicine.drug_class
Heart Ventricles
Blood Pressure
Pharmacology
Spironolactone
Losartan
Membrane Potentials
chemistry.chemical_compound
Angiotensin Receptor Antagonists
Mineralocorticoid receptor
Internal medicine
Hyperaldosteronism
Internal Medicine
medicine
Animals
Ventricular Function
Magnesium
Na+/K+-ATPase
Hyperaldosteronemia
Aldosterone
Mineralocorticoid Receptor Antagonists
Chemistry
Sodium
Eplerenone
Endocrinology
Mineralocorticoid
Potassium
Rabbits
Sodium-Potassium-Exchanging ATPase
medicine.drug
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 40
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....ae72e93b24fd96d2f8eaad02e05b9917