Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.
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Kinugawa T, Ogino K, Kato M, Furuse Y, Shimoyama M, Mori M, Endo A, Kato T, Omodani H, Osaki S, Miyakoda H, Hisatome I, Shigemasa C
Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.
Gen Pharmacol. 1998 Jul;31(1):93-9.
- PubMed ID
- 9595286 [ View in PubMed]
- Abstract
1. Treatment with spironolactone is reported to be useful when combined with loop diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effects of additive spironolactone on exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at rest and after peak exercise in nine patients with CHF (six idiopathic and three ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7 +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive single daily dose of 25 mg of spironolactone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P < 0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/- 2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/- 313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/- 11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and AII were insignificantly increased, and ANP was insignificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormones to return toward pretreatment values. 4. In conclusion, chronic additive treatment with spironolactone was associated with neurohormonal activation both at rest and during exercise without changing the exercise capacity of patients with mild CHF who were already on loop diuretics and ACE inhibitor therapy.
DrugBank Data that Cites this Article
- Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Spironolactone Approved NPPA 4878 decreased Spironolactone results in decreased expression of NPPA protein modified form 1p36.22 Spironolactone Approved REN 5972 increased Spironolactone results in increased expression of REN protein 1q32.1 Spironolactone Approved REN 5972 increased Spironolactone results in increased expression of REN protein 1q32.1 Spironolactone Approved AGT 183 increased Spironolactone results in increased expression of AGT protein modified form 1q42.2 Spironolactone Approved AGT 183 increased Spironolactone results in increased expression of AGT protein modified form 1q42.2