1. Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production
- Author
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Trung D. Tran, Bao Q. Do, Hoang M. Thai, Mohamed A. Gaballa, and Steven Goldman
- 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 - 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.
- Published
- 2005