title: Endotoxin enhances hypoxic constriction of rat aorta and pulmonary artery through induction of EDRF/NO synthase.
abstract: The vascular response to hypoxia in endotoxin (lipopolysaccharide; LPS)-exposed rat pulmonary artery (PA) and thoracic aorta (AO) was investigated and the mechanism of the observed hypoxic responses defined. In isometric tension studies, LPS-treated AO and PA rings, with and without endothelium, demonstrated decreased (P < 0.05) contractile response to phenylephrine (PE EC50), and the dose response was shifted to the right (P < 0.01) compared with non-LPS treated rings. Both vessel types responded to hypoxia with a markedly increased (P < 0.01) and sustained (P < 0.01) constriction when preexposed to LPS. Control non-LPS rings with endothelium intact had a transient vasoconstriction in early hypoxia, which was abolished with removal of the endothelium. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, increased the PE EC50 tension in LPS-treated rings, markedly reduced the duration and magnitude of the hypoxic vasoconstriction in LPS-treated rings, and attenuated the transient vasoconstriction seen in endothelium-intact, non-LPS rings (all P < 0.05). L-Arginine reversed the L-NAME effects. Hypoxia decreased guanosine 3',5'-cyclic monophosphate (cGMP) content 54 +/- 4% in all LPS and 33 +/- 4% in the non-LPS intact rings (P < 0.05). L-NAME reduced cGMP content 90 +/- 5% in all LPS rings. Indomethacin inhibited formation of a constriction factor in aortic LPS-treated rings (P < 0.01) that was endothelium dependent and unaffected by the presence of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: P
authors.initials: P
authors.lastname: Zelenkov
authors.forename: T
authors.initials: T
authors.lastname: McLoughlin
authors.forename: R A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001120:Arginine / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004790:Enzyme Induction; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D004731:Endotoxins; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D007213:Indomethacin