NMDA ALTERS THE DEVELOPMENT OF HYPOXIC PULMONARY VASOCONSTRICTION AND NITRIC OXIDE SYNTHETASE ACTIVITY IN THE ISOLATED PERFUSED RAT LUNG

Using an isolated salt-perfused rat lung model, the authors investigated whether N-methyl-D-aspartate (NMDA) (1 mM) in the pulmonary circulation effects the pulmonary vascular responses to an acute stimulus of hypoxic insult under baseline, nitric oxide synthetase (NOS)-blocked conditions (N- Ω -nitro-L arginine methyl ester; L-NAME, 2 mM), and with an NMDA receptor blocker, MK-801 (0.3 μ M) added. NOS activityat baseline, and in response tohypoxia, NMDA, L-NAME, and a combination of these stimuli were also assessed. NMDA did not in itself alter hypoxic pulmonary vasoconstriction (HPV), but did significantly attenuate HPV during NOS blockade. This effect of NMDA was erased by MK-801. Assessment of NOS activity showed that hypoxia alone caused a doubling of NO production within the lung. This effect was erased by the addition of L-NAME. NMDA alone caused a significant, 3-fold increase in NOS activity, which was not further affected by hypoxic challenge. L-NAME did not depress NOS activity in the hypoxia + ...