Differential inducible nitric oxide synthase expression in systemic and pulmonary vessels after endotoxin

Inducible nitric oxide synthase (iNOS) is associated with vascular hypocont ractility in systemic vessels after endotoxin lipopolysaccharide (LPS) admi nistration. Although lung iNOS is increased after LPS, its role in the pulm onary circulation is unclear. We hypothesized that whereas iNOS upregulatio n is responsible for LPS-induced vascular dysfunction in systemic vessels, iNOS does not play a significant role in the pulmonary artery (PA). Using i solated aorta (AO) and PA rings, we examined the effect of nonselective NOS inhibition [N-G-monomethyl-L-arginine (L-NMMA); 100 mu mol/l] and selectiv e iNOS inhibition (aminoguanidine, AG; 100 mu mol/l) on al-adrenergic-media ted vasoconstriction (phenylephrine; 10(-9) to 10(-3) M) after LPS (Salmone lla typhimurium, 20 mg/kg ip). We also determined the presence of iNOS usin g Western blot and immunohistochemistry. LPS markedly impaired AO contracti lity (maximal control tension 1,076 +/- 33 mg vs. LPS 412 +/- 39 mg, P < 0. 05), but PA contractility was unchanged (control 466 +/- 29 mg vs. LPS 455 +/- 27 mg, P > 0.05). Selective iNOS inhibition restored the AO's response to vasoconstriction (LPS + AG 1,135 +/- 54 mg, P > 0.05 vs, control and P < 0.05 vs. LPS), but had no effect on the PA(LPS + AG 422 +/- 38 mg, P > 0.0 5 vs. control and LPS). Western blot and immunohistochemistry revealed incr eased iNOS expression in the AO after LPS, but iNOS was not detected in the PA. Our results suggest that differential iNOS expression after LPS in sys temic and pulmonary vessels contributes to the phenomenon of sepsis/endotox emia-induced systemic hypotension and pulmonary hypertension.