Decreased production of vasodilators such as nitric oxide might contribute to the development of pulmonary hypertension. We previously found that pulmonary hypertension developed and that pulmonary vasodilation to the endothelium-dependent agent acetylcholine was blunted when newborn pigs were exposed to alveolar hypoxia (J. Appl. Physiol. 77:2853, 1994 and Ped. Res. 30:391A, 1994). The purpose of this study was to determine whether basal and acetylcholine stimulated production of nitric oxide are decreased in lungs of chronically hypoxic newborn pigs. We maintained 1-3 day old pigs in a chamber filled with either room air (Control) or 11% O2 (Chronic Hypoxia) for 10-12 days. Each pig was anesthetized and its lungs excised and perfused with 5% dextran at a constant flow of 50 (ml/min)/kg. Perfusate samples were collected at 15 min intervals for 90 min for measurement of basal nitrites and nitrates (NOx). Next, acetylcholine (10 μg/min) was infused and perfusate samples were collected at 10 min intervals for 30 min for measurement of acetylcholine stimulated NOx. Nitrate reduction and the Greiss reaction were used for NOx determination. Values intable are mean ± SE, *different from Control, unpaired t test, p<0.05. Both basal and acetylcholine stimulated rates of perfusate accumulation of NOx were lower in chronically hypoxic than in control lungs. These findings suggest that basal pulmonary production of nitric oxide and the ability to increase pulmonary production of nitric oxide in response to acetylcholine are decreased in newborn pigs exposed to chronic hypoxia. An impaired ability to increase nitric oxide production could explain why dilation to endothelium dependent agents such as acetylcholine are blunted in lungs of chronically hypoxic newborn pigs. It is possible that decreased basal pulmonary production of nitric oxide contributes to the development of pulmonary hypertension during chronic hypoxia in newborns. Supported by the American Heart Association and the Dept. of VA.

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