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


RESULTS
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.


CONCLUSIONS
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.
Thai
Hoang M
HM
Section of Cardiology, Department of Medicine, Southern Arizona VA Health Care System, Sarver Heart Center, University of Arizona, Tucson, 85723, USA.
Do
Bao Q
BQ
Tran
Trung D
TD
Gaballa
Mohamed A
MA
Goldman
Steven
S
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D019001:Nitric Oxide Synthase