AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 4 346-L354, Copyright © 1993 by American Physiological Society

ARTICLES

Endotoxin enhances hypoxic constriction of rat aorta and pulmonary artery through induction of EDRF/NO synthase

P. Zelenkov, T. McLoughlin and R. A. Johns
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.

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)

This article has been cited by other articles:

				T. A. Morinelli, J. G. Webb, A. A. Jaffa, P. J. Privitera, and H. S. Margolius A Metabolic Fragment of Bradykinin, Arg-Pro-Pro-Gly-Phe, Protects against the Deleterious Effects of Lipopolysaccharide in Rats J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 71 - 76. [Abstract] [Full Text]

				V. Hampl and J. Herget Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension Physiol Rev, October 1, 2000; 80(4): 1337 - 1372. [Abstract] [Full Text] [PDF]

				E. Cadogan, N. Hopkins, S. Giles, J. G. Bannigan, J. Moynihan, and P. McLoughlin Enhanced expression of inducible nitric oxide synthase without vasodilator effect in chronically infected lungs Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L616 - L627. [Abstract] [Full Text] [PDF]

				G. Salameh, M. R. Karamsetty, R. R. Warburton, J. R. Klinger, L. C. Ou, and N. S. Hill Differences in acute hypoxic pulmonary vasoresponsiveness between rat strains: role of endothelium J Appl Physiol, July 1, 1999; 87(1): 356 - 362. [Abstract] [Full Text] [PDF]

				S. Terraz, F. Baechtold, D. Renard, A. Barsi, A. Rosselet, A. Gnaegi, L. Liaudet, R. Lazor, J.-A. Haefliger, N. Schaad, et al. Hypoxic contraction of small pulmonary arteries from normal and endotoxemic rats: fundamental role of NO Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1207 - H1214. [Abstract] [Full Text] [PDF]

				M. Ozaki, C. Marshall, Y. Amaki, and B. E. Marshall Role of wall tension in hypoxic responses of isolated rat pulmonary arteries Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1069 - L1077. [Abstract] [Full Text] [PDF]

				S. R. FISCHER, D. J. DEYO, H. G. BONE, R. MCGUIRE, L. D. TRABER, and D. L. TRABER Nitric Oxide Synthase Inhibition Restores Hypoxic Pulmonary Vasoconstriction in Sepsis Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 833 - 839. [Abstract] [Full Text] [PDF]