The formation of nitric oxide (NO) by the endothelial isoform of NO synthase (eNOS) is inhibited by hypoxia in isolated pulmonary arteries. Additionally, incubation of pulmonary arteries with E. coli lipopolysaccharide (LPS) or heat inactivated group B Streptococcus (GBS) results in overproduction of NO as consequence of a marked increase in the inducible NOS (iNOS) activity. The purpose of the present study was to investigate whether incubation with LPS and GBS affected the contractile response to hypoxia in isolated intrapulmonary arteries (third branch) from 10-17 days old piglets. Arteries were incubated for 20 h in Krebs solution gassed with 21% O2 and 5% CO2 (pO2 145 ±1.27 mmHg) at 37°C in the presence of vehicle, E.coli LPS (1 μg /mL) or heat inactivated GBS (3 × 107 colonies forming units, cfu/mL) and isometric tension was recorded thereafter. The individual contractile response to 80 mM KCl was determined at the begining of the experiment. Hypoxia was generated in vascular rings precontracted with 30 mM KCl by switching the gas aerating the organ chambers from 21% O2 to 0% O2- 5% CO2(pO2 33.87 ±0.24 mmHg). The contractile response to 30 and 80 mM KCl was significantly reduced in LPS- and GBS-incubated arteries. This hyporresponsiveness was reversed by L-NAME. Hypoxia produced a transient endothelium-dependent vasoconstriction (387 ±55 mg; 33 ±4% of the 80 mM KCl-induced contraction) followed by a relaxation. The contraction in response to hypoxia was reduced in LPS- and GBS-incubated arteries (LPS: 168 ±34 mg; GBS: 184 ±37 mg P<0.05) but this reduction was proportional to the hyporresponsiveness to 80 mM KCl (LPS: 34 ±9%; GBS:42 ±11%). In conclusion, induction of iNOS by LPS and GBS in piglet pulmonary arteries produced a global reduction in the vessel responsiveness. The contractile response to hypoxia and KCl were similarly reduced in LPS- and GBS-incubated arteries suggesting that hypoxia did not affect the activity of iNOS.
