THE VEIN UTILIZES DIFFERENT SOURCES OF ENERGY THAN THE ARTERY DURING PULMONARY HYPOXIC VASOCONSTRICTION

Recent studies have shown that the contractile response to hypoxia is much greater in the pulmonary vein than in the artery. The purpose of this study was to investigate the effects of substrate utilization and oxidative phosphorylation. on the responses of the pulmonary vein and artery to acute hypoxia. Isolated rat pulmonary arterial and venous r ings were placed in tissue baths containing Earle's balanced salt solu tion (37 degrees C, 95% O-2/5% CO2, pH 7.4), and attached to force tra nsducers. The vascular rings were equilibrated for 1 h and then contra cted maximally with 80 mM KCl to establish maximum active tension deve lopment (P-o). Following washout and complete relaxation, the rings we re incubated with the following substrates or metabolic inhibitors for 30-40 min: varying concentrations of glucose (0, 5.5, 10, or 20 mM), or glycolytic intermediates (4 mM pyruvate or 4 mM lactate), or inhibi tors of glycolysis (50 mM 2-deoxyglucose or 0.1 mM iodoacetate), or an inhibitor of oxidative phosphorylation (0.1 mu M rotenone). Vascular rings were then made hypoxic by lowering the bath Po-2 to 30 torr. The pulmonary vein. responded with a single contraction while the artery responded biphasically as previously reported. The pulmonary venous hy poxic response was not affected by the absence of glucose but was inhi bited by high glucose concentrations. Neither glucose metabolic interm ediates (pyruvate or lactate) nor the glycolysis inhibitor 2-deoxygluc ose had any effect on the pulmonary venous response to hypoxia. Howeve r, inhibition of oxidative phosphorylation by rotenone inhibited the v enous hypoxic response. In contrast, the pulmonary arterial phase 1 co ntraction to hypoxia was inhibited and phase 2 contraction was abolish ed in glucose-free solution. This effect was not due to the decreased production of glucose metabolic intermediates, since addition of pyruv ate or lactate did not reverse the decreased arterial hypoxic response in glucose-free solution. Increasing the glucose concentration did no t affect phase 1 contraction, but 20 mM glucose inhibited the phase 2 contraction. Inhibition of glycolysis with 2-deoxyglucose or iodoaceta te decreased phase 1 contraction and abolished the phase 2 contraction . Inhibition of oxidative ATP production with rotenone abolished phase 1 but not phase 2 contraction. In conclusion, (1) the pulmonary venou s response to hypoxia is unaffected by inhibition. of glycolysis but i s inhibited by high glucose and by inhibition of oxidative ATP product ion; (2) the pulmonary arterial hypoxic phase 1 contraction is depende nt on oxidative ATP production; and (3) the phase 2 contraction of the pulmonary arterial hypoxic response depends on glycolytic ATP product ion but not on oxidative ATP production. These results indicate that t he pulmonary vein and artery preferentially utilize different sources of energy for hypoxic contractions.