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Effects of angiotensin II type 1 receptor antagonist, losartan, on ventilatory response to exercise and neurohormonal profiles in patients with chronic heart failure.

Chronic heart failure (CHF) is associated with abnormal neurohormonal profiles and increased ventilatory response to exercise. This study determined if treatment with angiotensin II type 1 receptor antagonist, losartan, improves ventilatory efficiency and neurohormonal factors in patients with CHF. Symptom-limited cardiopulmonary exercise testing was performed after a 2-week placebo period (baseline) and after 16 weeks of treatment with losartan (40 +/- 4 mg/day) in 10 patients with CHF (age 57.7 +/- 3.7 years). Echocardiogram, daily physical activity (by the specific activity scale), and neurohormones were evaluated. Treatment with losartan increased left ventricular ejection fraction (baseline vs. losartan: 31 +/- 3 vs. 39 +/- 3%, p<0.01) and specific activity scale score (5.3 +/- 0.5 vs. 6.4 +/- 0.4 METS, p<0.05). Losartan decreased the ventilatory response to carbon dioxide production during exercise (VE/VCO2 slope: 34.6 +/- 2.4 vs. 32.0 +/- 2.2, p<0.05). Plasma brain natriuretic peptide concentrations were decreased after therapy (301 +/- 79 vs. 176 +/- 53 pg/ml, p<0.05). In summary, the results of this open-label, uncontrolled study suggest that chronic treatment with losartan may improve ventilatory efficiency and decrease plasma brain natriuretic peptide concentrations with the improvement of physical activity and left ventricular systolic function in patients with CHF.