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

The present study was aimed at examining the role of nitric oxide (NO) in t he hypoxic contraction of isolated small pulmonary arteries (SPA) in the ra t. Animals were treated with either saline (sham experiments) or Escherichi a coli lipolysaccharide [LPS, to obtain expression of the inducible NO synt hase (iNOS) in the lung] and killed 4 h later. SPA(300- to 600-mu m outer d iameter) were mounted as rings in organ chambers for the recording of isome tric tension, precontracted with PGF(2 alpha), and exposed to either severe (bath PO2 8 +/- 3 mmHg) or milder (21 +/- 3 mmHg) hypoxia. In SPA from sha m-treated rats, contractions elicited by severe hypoxia were completely sup pressed by either endothelium removal or preincubation with an NOS inhibito r [N-G-nitro-L-arginine methyl ester (L-NAME), 10(-3) M]. In SPA from LPS-t reated 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 resul ts indicate an essential role of NO in the hypoxic contractions of precontr acted rat SPA. The endothelium independence of HPV in arteries from LPS-tre ated animals appears related to the extraendothelial expression of iNOS. Th e severe degree of hypoxia required to elicit any contraction is consistent with a mechanism of reduced NO production caused by a limited availability of O-2 as a substrate for NOS.