Hypoxic pulmonary vasoconstriction increases during endotoxemia in the perfused rat lung.
BACKGROUND
Several investigations have studied hypoxic pulmonary vasoconstriction (HPV) during endotoxemia, as in this situation there is an increase in the activation of the inducible nitric oxide synthases, producing a greater liberation of nitric oxide (NO) in the pulmonary vessels. However, these studies yielded conflicting or at times contradictory results, since reference has been made to both enhancement and inhibition of HPV. Our objective was to determine the effect of hypoxia on the isolated blood-perfused lung of endotoxemic rats, and to give at least a partial explanation of its production mechanism.


METHODS
Pulmonary arterial pressure (PAP) was measured in a blood-perfused lung preparation from Wistar rats in normoxia (O2, 20%; CO2, 5%; N, 75%) and hypoxia (O2, 2%; CO2, 5%; N, 93%). There were three experimental protocols. We studied the effect of hypoxia in a control group (CG) and an endotoxemic 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 blue (MB) on two subgroups of groups CG (CGnmla and CGmb) and EG (EGnmla and EGmb). With the exception of the CG, all specimens were pretreated with a 20-mg/kg intraperitoneal injection of Escherichia coli lipopolysaccharide.


RESULTS
DeltaPAP elicited by hypoxia in the EG group (15.90 +/- 4.75 mm Hg) was 2.30 times higher than in the CG (6.89 +/- 1.96 mm Hg). In the E+IG group, hypoxia produced a DeltaPAP of 15.20 +/- 3.56 mm Hg, similar to that in the EG. The addition of MB in the EGmb subgroup increased base PAP during normoxia from 19.1 +/- 1.23 mm Hg to 32.2 +/- 6.1 mm Hg (p < 0.05).


CONCLUSIONS
In an isolated-perfused rat model, E. coli lipopolysaccharide (20 mg/kg) significantly increased HPV. This response is maintained over time. Inhibition of NO release by hypoxia may be responsible for the enhanced HPV after endotoxin.
Castañeda
J
J
Department of Surgery, Intensive Care Unit, University Hospital of Valladolid, C/Ramón y Cajal s/n, 47005 Valladolid, Spain.
Isusi
A
A
Tamayo
L
L
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D023421:Models, Animal; D010477:Perfusion; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction
D004731:Endotoxins