Pediatric research
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This study was carried out to determine the influence and site of action of N omega-nitro-L-arginine methylester, an L-arginine analogue, on basal pulmonary vascular tone and hypoxic vasoconstriction in neonatal pig lungs. We studied isolated lungs from pigs, age 14.5 +/- 0.5 (SD) d and weight 3.6 +/- 0.7 kg, perfused with autologous blood at a constant flow rate. The arterial-venous occlusion method was used to determine sites of action upstream and downstream of the double occlusion pressure (Pd) during baseline, infusion of acetylcholine, and ventilation of the lung with a hypoxic gas mixture. ⋯ Infusion of acetylcholine resulted in downstream dilation, and hypoxia resulted in an increase in both upstream and downstream resistance. After adding N omega-nitro-L-arginine methylester to the blood, there was an increase in both upstream and downstream resistances; acetylcholine infusion resulted in an increase in total vascular resistance, which was entirely due to upstream constriction; and the hypoxia response was much larger both upstream and downstream of Pd. These results suggest that nitric oxide synthase helped maintain a low level of basal pulmonary vascular tone both upstream and downstream of Pd in these neonatal pig lungs; that the vascular effect of acetylcholine was changed from downstream dilation to upstream constriction by N omega-nitro-L-arginine methylester; and that nitric oxide synthase activity modulated both the upstream and downstream vasomotor response to hypoxia.