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(ω)-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. These data confirm that the transient hypoxic constriction seen in non-LPS-treated vascular rings is due to hypoxic inhibition of constitutive NO synthase found in endothelium and demonstrate that the inhibition by hypoxia of LPS-induced NO synthase is the primary mechanism of the enhanced and sustained hypoxic vasoconstriction seen in LPS- treated vessels.
Original language | English (US) |
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Pages (from-to) | L346-L354 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 265 |
Issue number | 4 9-4 |
DOIs | |
State | Published - 1993 |
Externally published | Yes |
Keywords
- N(ω)-nitro-L-arginine methyl ester
- arachidonic acid
- endothelium-derived relaxing factor
- hypoxia
- indomethacin
- lipopolysaccharide
- nitric oxide
- nitric oxide synthase
- sepsis
- thoracic aorta
- vasoconstriction
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology