Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production

Journal of Cardiac Failure
Hoang M ThaiSteven Goldman

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.

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Citations

Dec 27, 2011·Cellular and Molecular Neurobiology·Kirtiman SrivastavaUlvi Bayraktutan
Feb 5, 2011·Heart Failure Reviews·Dimitris TousoulisChristodoulos Stefanadis
Jul 5, 2011·Molecular and Cellular Endocrinology·Amy McCurley, Iris Z Jaffe
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Jul 28, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Ikeotunye Royal ChinyereElizabeth Juneman

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