ROLE OF EDRF IN PULMONARY CIRCULATION DURING SUSTAINED HYPOXIA

The pulmonary artery pressure (PAP) response to hypoxia is characteriz ed by an initial vasoconstriction followed by vasodilation. Pulmonary vessels can release endothelium-derived relaxing factor (EDRF), which is considered to be nitric oxide (NO), but the role of EDRF in the reg ulation of normal and hypoxic pulmonary vascular tone is still uncerta in. We designed this study to address the in vivo role of EDRF in vaso dilation during sustained hypoxia. We studied the effects of an EDRF-s ynthesis inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), on the pulmonary vascular response to sustained hypoxia (10% O-2, 20 min ) in normoxic (N) and chronically hypoxic (CH) rats. Biphasic PAP resp onse was observed in N rats, whereas PAP was unchanged in CH rats duri ng sustained hypoxic exposure. The L-NAME-induced PAP increase during normoxia was greater in CH than in N rats, suggesting that basal EDRF plays an important role in attenuating the severity of pulmonary hyper tension in CH rats. Administration of L-NAME increased the initial inc rement in PAP by acute hypoxia and shifted the PAP response upward thr oughout sustained hypoxia, while still showing the biphasic pattern, i n N rats. In contrast, PAP increased acutely and remained elevated wit h little recovery in the late phase in CH rats. The inducible NO synth ase messenger RNA (mRNA) expression and protein showed greater increas es in the lungs of CH than in N rats. These results suggest that EDRF release during sustained hypoxia may partly contribute to the roll-off in PAP response during sustained hypoxia in N rats, and that augmente d EDRF may prevent a further increase in PAP during chronic hypoxia.