L‐Citrulline Inhibits Chronic Hypoxia‐Induced Pulmonary Hypertension in Newborn Piglets

Abstract

Decreased Nitric Oxide (NO) production may contribute to the development of chronic hypoxia‐induced PHT. NO is produced from arginine by nitric oxide synthase. Citrulline is metabolized to arginine and may increase the amount of arginine available for NO production. Our goal was to determine if supplementation with L‐citrulline inhibits chronic hypoxia‐induced PHT in newborn pigs. Two day old pigs were kept in hypoxia (H, n=15) or normoxia (controls, C, n=5) for 10 days. Some (n=5) H pigs received oral L‐citrulline (0.13 mg/kg/dose bid). Catheters were placed to measure pulmonary artery pressure (Ppa), left ventricular end diastolic pressure, cardiac output by thermodilution and exhaled NO concentration (ppb). Ppa (cm H2O) and pulmonary vascular resistance (PVR, cmH2O.ml−1.min−1.kg−1) were higher in untreated H (Ppa 39±3, PVR 0.13±0.01) than C (Ppa 21±3, PVR 0.04±0.01) piglets. Ppa and calculated PVR in citrulline‐treated H (Ppa 27±1, PVR 0.07±0.004) did not differ from C. Values for exhaled NO were lower in untreated H (1.5 ±0.2) than C (3.4±0.6) but did not differ between citrulline‐treated H (2.5±0.4) and C pigs. Thus, L‐citrulline increases NO production and inhibits the development of PHT in piglets exposed to 10 days chronic hypoxia. We speculate that enteral supplementation with L‐citrulline may limit pulmonary vascular changes in neonates who have prolonged periods of hypoxia. Supported: AHA‐SE Affil