L-Arginine increases nitric oxide production in isolated lungs of chronically hypoxic newborn pigs

Previously, our laboratory found that pulmonary hypertension developed and lung nitric oxide (NO) production was reduced when piglets were exposed to chronic hypoxia (Fike CD, Kaplowitz MR, Thomas CJ, and Nelin LD. Am J Physi ol Lung Cell Mol Physiol 274: L517-L526, 1998). The purposes of this study were to determine whether L-arginine addition augments NO production and to evaluate whether L-arginine uptake is impaired in isolated lungs of chroni cally hypoxic newborn piglets. Studies were performed by using 1- to 3-day- old piglets raised in room air (control) or 10% O-2 (chronic hypoxia) for 1 0-12 days. Lung NO production was assessed in isolated lungs from both grou ps by measuring the perfusate accumulation of nitrites and nitrates (collec tively termed NOx-) before and after addition of L-arginine (10(-2) M) to t he perfusate. The rate of perfusate NO; accumulation increased by 220% (fro m 0.8 +/- 0.4 to 2.5 +/- 0.5 nmol/min, P < 0.05) after L-arginine addition to chronic hypoxic lungs but remained unchanged (3.2 +/- 0.8 before vs. 3.3 +/- 0.4 nmol/min after L-arginine) in control lungs. In the second series of studies, L-arginine uptake was evaluated by measuring the perfusate conc entration of L- [H-3] arginine at fixed time intervals. The perfusate conce ntration of L-[H-3]arginine at each time point was less (P < 0.05) in contr ol than in chronic hypoxic lungs. Thus L-arginine uptake was impaired and m ay underlie in part the reduction in lung NO production that occurs when pi glets are exposed to 10-12 days of chronic hypoxia. Moreover, these finding s in isolated lungs lead to the possibility that L-arginine supplementation might increase in vivo lung NO production in piglets with chronic hypoxia- induced pulmonary hypertension.