Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy

Abiose, Ademola K.; Mansoor, George A.; Barry, Marybeth; Soucier, Richard; Nair, Chandra K.; Hager, David

doi:10.1016/j.amjcard.2004.03.015

Cited by 45 publications

(33 citation statements)

References 16 publications

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“…[1,9,[25][26][27][28][29][30][31][32][33] For example, the patients included in earlier spironolactone heart failure studies were sicker (and thus probably had more pronounced neuroendocrine activation), [1] the dose of spironolactone was usually higher (50-100 mg) than in our own study, [29] and fewer patients in these studies received a beta-blocker [1,9,[25][26][27][28][29][30][31][32][33]. Furthermore, the small sample size and limited power of our own study may have contributed to some of our neutral findings [30].…”

Section: Discussionmentioning

confidence: 63%

Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker

Berry

Murphy

Vito

et al. 2007

European J of Heart Fail

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Aims: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. Methods and results: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of b 40%.The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) − 53.4(22.2) pg/mL and + 3.3(12.1) pg/mL, P = 0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) −0.6(0.2) μmol/L and + 0.02(0.2) μmol/L, P = 0.02 and iii) creatinine + 10.7(3.2) μmol/L and −0.3(2.6) μmol/L, P = 0.01.Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: −6 (3) vs. + 6 (4); P = 0.01.No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. Conclusion: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.

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Section: Discussionmentioning

confidence: 63%

Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker

Berry

Murphy

Vito

et al. 2007

European J of Heart Fail

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“…Other therapies that improve HF survival and EF also improve endothelial function (Fig. 4, Table 1 [201][202][203][204][205][206][207][208][209][210][211][212][213][214][215][216]). Angiotensin-converting enzyme (ACE) inhibitors improve endothelial function through enhancing bradykinin and reducing oxidative stress (205,217).…”

Section: Strategies To Improve Endothelial Function In Hfmentioning

confidence: 99%

Endothelial Dysfunction, Arterial Stiffness, and Heart Failure

Marti

Gheorghiade

Καλογερόπουλος

et al. 2012

Journal of the American College of Cardiology

390

274

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Outcomes for heart failure (HF) patients remain suboptimal. No known therapy improves mortality in acute HF and HF with preserved ejection fraction; the most recent HF trial results have been negative or neutral. Improvement in surrogate markers has not necessarily translated into better outcomes. To translate breakthroughs with potential therapies into clinical benefit, a better understanding of the pathophysiology establishing the foundation of benefit is necessary. Vascular function plays a central role in the development and progression of HF. Endothelial function and nitric oxide availability affect myocardial function, systemic and pulmonary hemodynamics, and coronary and renal circulation. Arterial stiffness modulates ventricular loading conditions and diastolic function, key components of HF with preserved ejection. Endothelial function and arterial stiffness may therefore serve as important physiological targets for new HF therapies and facilitate patient selection for improved application of existing agents.

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“…33 This could be one mechanism why Abiose et al found an improved flow-mediated dilation after treatment with spironolactone in heart failure patients. 8 The influence of aldosterone antagonism on nongenomic effects is another unsolved issue. Whether eplerenone leads to more complete inhibition of nongenomic aldosterone effects than spironolactone by blocking a not yet defined additional aldosterone receptor, 35,36 remains uncertain.…”

Section: Nietlispach Et Al Aldosterone and Its Role In Vasomotionmentioning

confidence: 99%

Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men

et al. 2007

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Abstract-Aldosterone has rapid nongenomic effects in the human vasculature. However, data are not uniform and little is known about chronic effects of aldosterone. Therefore, we investigated acute and chronic effects of elevated aldosterone levels on endothelial function in the forearm vasculature of healthy men. In a first crossover study, the effects of arterial aldosterone infusion in ascending doses (3.3 to 55 pmol/min per 1000 mL forearm volume) on forearm blood flow were investigated in 8 healthy men (26Ϯ2 years). In a second study, endothelium-dependent (acetylcholine; 0.08, 0.275, and 2.75 mol/min per 1000 mL) and endothelium-independent (sodium nitroprusside 0.02 mol/min per 1000 mL) vasodilation and basal nitric oxide formation (forearm blood flow response to blockade by N G -monomethyl-L-arginine 8 mol/min per 1000 mL) were tested in 10 healthy men (age 30Ϯ5 years) at baseline, during infusion of 55 pmol/1000 mL per min aldosterone (acute effects), and after 0.3 mg/d oral fludrocortisone for 2 weeks (chronic effects) on separate days. Forearm blood flow was assessed by venous occlusion plethysmography. No change in forearm blood flow was seen with aldosterone infusion alone. Acute coinfusion of aldosterone increased vasodilation to sodium nitroprusside by 93% (PϽ0.01) and to acetylcholine by 60% (Pϭ0.14). Response to N G -monomethyl-L-arginine did not change. After 2 weeks of oral fludrocortisone, response to acetylcholine was enhanced by 72% compared with baseline (Pϭ0.03). Additionally, response to N G -monomethyl-L-arginine was enhanced by 80% compared with baseline (Pϭ0.05). Aldosterone acutely enhances vasodilation to exogenous nitric oxide whereas mineralocorticoid excess for 2 weeks enhances basal nitric oxide bioactivity and improves endothelium dependent, nitric oxide-mediated vasodilation in the forearm vasculature of healthy men. Key Words: aldosterone Ⅲ endothelial function Ⅲ mineralocorticoid excess Ⅲ forearm vasculature Ⅲ nitric oxide A ldosterone has been claimed to lead to endothelial dysfunction (review, see Brown 1 ), a condition related to development of cardiovascular disorders and to poor prognosis. 2 However, studies of aldosterone effects on endothelial function led to discrepant findings, which may be related, at least in part, to inhomogeneity of the populations studied. Thus, studies in healthy subjects showed no detrimental effects of aldosterone on endothelial function and no positive effect of aldosterone inhibition, 3-5 whereas populations with established cardiovascular diseases showed negative effects of aldosterone and positive effects of spironolactone therapy. 6 -11 Still, other factors may be of importance as effects of aldosterone on endothelial function are not homogenous even in a healthy population. 12 Dosages of aldosterone, 3,4,6 concomitant drug use, 13 as well as the vascular bed investigated 5,14 -16 may influence the effects observed.Furthermore, little is known about chronic endothelial effects of aldosterone that could indicate a primary and direct role...

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Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy

Cited by 45 publications

References 16 publications

Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker

Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker

Endothelial Dysfunction, Arterial Stiffness, and Heart Failure

Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men

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