Short-term Oral Administration of l-Arginine Improves Hemodynamics and Exercise Capacity in Patients with Precapillary Pulmonary Hypertension

Abstract
We sought to assess the effects of oral supplementation of l-arginine, the precursor of nitric oxide (NO), on hemodynamics and exercise capacity in patients with pulmonary hypertension. Acute hemodynamic responses to oral l-arginine (0.5 g/10 kg body weight) or placebo were examined in 19 patients with primary or precapillary secondary pulmonary hypertension. Cardiopulmonary exercise tests were performed to measure peak oxygen consumption (peak V˙ o 2) and the ventilatory response to carbon dioxide production (V˙ e-V˙ co 2 slope) before and 1 wk after treatment with l-arginine (1.5 g/10 kg body weight/d) or placebo. Oral supplementation of l-arginine significantly increased plasma l-citrulline, which indicated enhancement of NO production. Supplemental l-arginine produced a 9% decrease in mean pulmonary arterial pressure (53 ± 4 to 48 ± 4 mm Hg, p < 0.05) and a 16% decrease in pulmonary vascular resistance (14.8 ± 1.5 to 12.4 ± 1.4 Wood units, p < 0.05). l-arginine modestly decreased mean systemic arterial pressure (92 ± 4 to 87 ± 3 mm Hg, p < 0.05). A 1-wk supplementation of l-arginine resulted in a slight increase in peak V˙ o 2 (831 ± 88 to 896 ± 92 ml/min, p < 0.05) and a significant decrease in the V˙ e-V˙ co 2 slope (43 ± 4 to 37 ± 3, p < 0.05) without significant systemic hypotension. Hemodynamics and exercise capacity remained unchanged during placebo administration. These results suggest that oral supplementation of l-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.