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Am J Physiol Heart Circ Physiol 276: H1207-H1214, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 4, H1207-H1214, April 1999

Hypoxic contraction of small pulmonary arteries from normal and endotoxemic rats: fundamental role of NO

Sylvain Terraz1, François Baechtold1, Delphine Renard1, Attila Barsi1, Anne Rosselet1, Alex Gnaegi1, Lucas Liaudet1, Romain Lazor1, Jacques-A. Haefliger2, Nicolas Schaad5, Claude Perret1, Paul Kucera4, Michèle Markert3, and Francois Feihl1

1 Division of Clinical Pathophysiology and 2 Laboratory of Molecular Biology, Department of Internal Medicine, and 3 Central Laboratory of Clinical Chemistry, Lausanne University Hospital, 1011 Lausanne; 4 Institute of Physiology, Lausanne University Medical School, 1005 Lausanne; and 5 Pharmacie Interhospitalière de La Côte, 1110 Morges, Switzerland

The present study was aimed at examining the role of nitric oxide (NO) in the hypoxic contraction of isolated small pulmonary arteries (SPA) in the rat. Animals were treated with either saline (sham experiments) or Escherichia coli lipolysaccharide [LPS, to obtain expression of the inducible NO synthase (iNOS) in the lung] and killed 4 h later. SPA (300- to 600-µm outer diameter) were mounted as rings in organ chambers for the recording of isometric tension, precontracted with PGF2alpha , and exposed to either severe (bath PO2 8 ± 3 mmHg) or milder (21 ± 3 mmHg) hypoxia. In SPA from sham-treated rats, contractions elicited by severe hypoxia were completely suppressed by either endothelium removal or preincubation with an NOS inhibitor [NG-nitro-L-arginine methyl ester (L-NAME), 10-3 M]. In SPA from LPS-treated rats, contractions elicited by severe hypoxia occurred irrespective of the presence or absence of endothelium and were largely suppressed by L-NAME. The milder hypoxia elicited no increase in vascular tone. These results indicate an essential role of NO in the hypoxic contractions of precontracted rat SPA. The endothelium independence of HPV in arteries from LPS-treated animals appears related to the extraendothelial expression of iNOS. The severe degree of hypoxia required to elicit any contraction is consistent with a mechanism of reduced NO production caused by a limited availability of O2 as a substrate for NOS.

pulmonary circulation; hypoxia; vascular endothelium; nitric oxide; endotoxin; rat


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