Septicemia-enhanced Nitric Oxide Synthase (NOS) activity in pulmonary vein

Septicemia increases intrapulmonary shunt fraction and blocks pulmonary hypoxic vasoconstriction in sheep. We have shown that these pulmonary effects of sepsis are blocked by inhibitors of NOS. The purpose of the present study was to determine the effect of sepsis on the contractile reactivity and NOS activity in isolated pulmonary veins (PV). Third order PV were collected from chronically instrumented sheep: healthy (n=6) and septic (24h infusion of 6108 colony-forming units/kg/h Ps. aeruginosa, n=6). For contractile studies, ring segments (3mm) were mounted by 2 triangular wires in 100ml baths containing Krebs-bicarbonate solution at 37°C. NOS activity was measured using the ³H-I-arginine to ³H-I-citrulline conversion assay and reported as pmol/mg protein/min. Norepinephrine (NE,10μM) produced significantly (p<0.05) lower contractions in septic PV (192.5±59.9mg) compared to healthy PV (363.3±80.9mg). The total NOS activity was 3.6 times greater (p<0.05) in the septic PV (16.6±2.3) than in the healthy PV (4.7±0.9). The calcium-independent (0Ca) NOS activity (reflecting INOS activity) was 2.4 times greater (p<0.05) in the septic PV (7.0±4.2) than in healthy PV (2.9±1.0). The NOS inhibitors I-nitro I-arginine methyl ester (LNAME) and aminoguanidine inhibited, respectively, total NOS and 0Ca NOS activities in septic and healthy PV. The results suggests the possibility that sepsis-induced depression of pulmonary venous constriction, mediated by NO, is involved in the inhibition of hypoxic vasoconstriction that is essential for a proper ventilation-perfusion ratio.