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-omega-nitro-L arginine methyl ester; L-NAME, 2 mM), and with an NMDA receptor blocker, MK-801 (0.3 microM) added. NOS activity at baseline, and in response to hypoxia, 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 VOS 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 chalenge. L-NAME did not depress NOS activity in the hypoxia + NMDA group. These data suggest that NMDA receptor activation results in increased NOS activity and presumably increased production of NO. The increased NOS activity induced by NMDA receptor stimulation is resistant to the blockade effect of L-NAME. The actions of NMDA receptor activation may represent a natural protective mechanism, at least within the pulmonary vasculature, in face of acute, abnormal stimuli such as hypoxia.
Polak
Mark J
MJ
Department of Pediatrics, West Virginia University School of Medicine, Morgantown 26506, USA. MPOLAK@HSC.WVU.EDU
Xiao
Shen
S
Ashton
Christopher A
CA
Baylis
Christine
C
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester