Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the effects of exposure of the lung to hyperoxic conditions on reactivity of pulmonary microcirculation to hypoxic stimulation, we measured hypoxia-elicited overall pulmonary pressor changes (HPV) and microvascular diameter changes in intraacinar arterioles, venules, and capillaries in isolated perfused rat lungs exposed to a hyperoxic environment (90% O2). To estimate the importance of vasoactive prostaglandins and nitric oxide (NO) for HPV modification, we examined the roles of constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2) and those of NO synthase (eNOS and iNOS). Indomethacin was used for inhibiting both COX-1 and COX-2, while NS-398 was used as a selective inhibitor of COX-2. Both eNOS and iNOS were suppressed by L-NAME, whereas iNOS alone was inhibited by aminoguanidine. Microvascular diameter was measured with a real-time confocal laser scanning luminescence microscope. We found that (1) exposure to hyperoxia caused overall HPV and arteriolar constriction to be attenuated; (2) the blunted HPV was restored by L-NAME but not by aminoguanidine, indomethacin, or NS-398; and (3) arteriolar constriction was improved by either L-NAME, aminoguanidine, or indomethacin but only slightly by NS-398. In conclusion, attenuation of overall HPV in hyperoxia-exposed lungs is explicable mainly by excessive NO generated via eNOS, while impaired arteriolar constriction is caused by NO yielded by eNOS and iNOS as well as by vasodilating prostaglandin(s) produced by COX-1.
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PMID:Impaired hypoxic vasoconstriction in intraacinar microvasculature in hyperoxia-exposed rat lungs. 970 Jan 41

The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). Real-time confocal luminescence microscopy was used to measure changes in the diameter of acinar arterioles, venules and capillaries in response to stimulation with hypercapnic and isocapnic acidosis in isolated rat lungs injured by 90% oxygen exposure for 48 h. Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX-1) and inducible isoforms (iNOS and COX-2) of NOS and COX. Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6-ketoprostaglandin F1alpha. ecNOS and COX-1, but not iNOS and COX-2, were upregulated in hyperoxia-injured lungs. The nitric oxide produced by ecNOS attenuated COX-1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. Although a high hydrogen ion concentration was unnecessary for excitation of COX-1, venule constriction in response to H+ was enhanced by COX-1 inhibition. Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs.
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PMID:NOS and COX isoforms and abnormal microvessel responses to CO2 and H+ in hyperoxia-injured lungs. 1216 83