Hypoxic pulmonary vasoconstriction increases during endotoxemia in the perfused rat lung

Background: several investigations have studied hypoxic pulmonary vasoconst riction (HPV) during endotoxemia, as in this situation there is an increase in the activation of the inducible nitric oxide synthases, producing a gre ater liberation of nitric oxide (NO) in the pulmonary vessels. However, the se studies yielded conflicting or at times contradictory results, since ref erence has been made to both enhancement and inhibition of HPV, Our Objecti ve was to determine the effect of hypoxia on the isolated blood-perfused lu ng of endotoxemic rats, and to give at least a partial explanation of its p roduction mechanism. Methods: Pulmonary arterial pressure (PAP) was measured in a blood-perfused lung preparation from Wistar rats in normoxia (O-2, 20%; CO2, 5%; N, 75%) and hypoxia (O-2, 2%; CO2, 5%; N, 93%). There were three experimental proto cols. We studied the effect of hypoxia in a control group (CG) and an endot oxemic group (EG), Second, we studied the effect of hypoxia in endotoxemic rats pretreated with indomethacin (E+IG), Third, we assessed the effect of two inhibitors of NO synthesis: N-methyl-L-arginine (NMLA) and methylene bl ue (MB) on two subgroups of groups CG (CG(NMLA) and CG(MB)) and EG (EG(NMLA ) and EG(MB)). With the exception of the CG, all specimens were pretreated with a 20-mg/kg intraperitoneal injection of Escherichia coli lipopolysacch aride Results: Delta PAP elicited by hypoxia in the EG group (15.90 +/- 4.75 mm B g) was 2.30 times higher than in the CG (6.89 +/- 1.96 mm Hg). In the E+IG group, hypoxia produced a Delta PAP of 15.20 +/- 3.56 mm Hg, similar to tha t in the EG, The addition of MB in the EG(MB) subgroup increased base PAP d uring normoxia from 19.1 +/- 1.23 mm Hg to 32.2 +/- 6.1 mm Hg (p < 0.05). Conclusion: In an isolated-perfused rat model, E. coli lipopolysaccharide ( 20 mg/kg) significantly increased HPV, This response is maintained over tim e, Inhibition of NO release by hypoxia mag. be responsible for the enhanced HPV after endotoxin.