Am. J. Respir. Crit. Care Med., Volume 163, Number 4, March 2001, 887-891

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

NORITOSHI NAGAYA, MASAAKI UEMATSU, HIDEO OYA, NAGATO SATO, FUMIO SAKAMAKI, SHINGO KYOTANI, KAZUYUKI UENO, NORIFUMI NAKANISHI, MASAKAZU YAMAGISHI, and KUNIO MIYATAKE

Department of Internal Medicine and Department of Pharmacy, National Cardiovascular Center, and Osaka Seamen's Insurance Hospital, Osaka, Japan

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 O₂) and the ventilatory response to carbon dioxide production ( E- CO₂ 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 O₂ (831 ± 88 to 896 ± 92 ml/min, p < 0.05) and a significant decrease in the E- CO₂ 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.

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