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Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production
- Source :
- Journal of cardiac failure. 12(3)
- Publication Year :
- 2005
-
Abstract
- Altering the renin-angiotensin aldosterone system improve mortality in heart failure (HF) in part through an improvement in nitric oxide (NO)-mediated endothelial function. This study examined if spironolactone affects endothelial nitric oxide synthase (eNOS) and NO-mediated vasorelaxation in HF.Rats with HF after coronary artery ligation were treated with spironolactone for 4 weeks. Rats with HF had a decrease (P.05) in left ventricular (LV) systolic pressure (130 +/- 7 versus 118 +/- 6 mm Hg) and LV pressure with respect to time (9,122 +/- 876 versus 4,500 +/- 1971 mm Hg/second) with an increase in LV end-diastolic pressure (4 +/- 2 versus 23 +/- 8 mm Hg). Spironolactone did not affect hemodynamics but it improved (P.05) endothelial-dependent vasorelaxation at more than 10(-8) M acetylcholine that was abolished with N(G)-monomethyl-L-arginine. The eNOS levels were decreased (P.05) in the LV and the aorta; spironolactone restored LV and aortic eNOs levels to normal.Spironolactone prevents the decrease in eNOS in the LV and aorta and improves NO-dependent vasorelaxation, suggesting that one potential mechanism of spironolactone is an improvement in vasoreactivity mediated though an increase in NO.
- Subjects :
- Male
medicine.medical_specialty
Vasodilation
Spironolactone
Nitric oxide
Rats, Sprague-Dawley
Renin-Angiotensin System
chemistry.chemical_compound
Mineralocorticoid receptor
Enos
Internal medicine
Renin–angiotensin system
medicine
Animals
Mineralocorticoid Receptor Antagonists
Heart Failure
Aldosterone
biology
business.industry
Hemodynamics
biology.organism_classification
Rats
Nitric oxide synthase
Endocrinology
chemistry
biology.protein
Endothelium, Vascular
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 15328414
- Volume :
- 12
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of cardiac failure
- Accession number :
- edsair.doi.dedup.....7aba3597ff5d3dfbda482c988187a3e7