title: The vein utilizes different sources of energy than the artery during pulmonary hypoxic vasoconstriction.
abstract: 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 rings were placed in tissue baths containing Earle's balanced salt solution (37 degrees C, 95% O2/5% CO2, pH 7.4), and attached to force transducers. The vascular rings were equilibrated for 1 h and then contracted maximally with 80 mM KCl to establish maximum active tension development (Po). Following washout and complete relaxation, the rings were 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 inhibitors of glycolysis (50 mM 2-deoxyglucose or 0.1 mM iodoacetate), or an inhibitor of oxidative phosphorylation (0.1 microM rotenone). Vascular rings were then made hypoxic by lowering the bath Po2 to 30 torr. The pulmonary vein responded with a single contraction while the artery responded biphasically as previously reported. The pulmonary venous hypoxic response was not affected by the absence of glucose but was inhibited by high glucose concentrations. Neither glucose metabolic intermediates (pyruvate or lactate) nor the glycolysis inhibitor 2-deoxyglucose had any effect on the pulmonary venous response to hypoxia. However, inhibition of oxidative phosphorylation by rotenone inhibited the venous hypoxic response. In contrast, the pulmonary arterial phase 1 contraction to hypoxia was inhibited and phase 2 contraction was abolished in glucose-free solution. This effect was not due to the decreased production of glucose metabolic intermediates, since addition of pyruvate or lactate did not reverse the decreased arterial hypoxic response in glucose-free solution. Increasing the glucose concentration did not affect phase 1 contraction, but 20 mM glucose inhibited the phase 2 contraction. Inhibition of glycolysis with 2-deoxyglucose or iodoacetate 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 venous response to hypoxia is unaffected by inhibition of glycolysis but is inhibited by high glucose and by inhibition of oxidative ATP production; (2) the pulmonary arterial hypoxic phase 1 contraction is dependent on oxidative ATP production; and (3) the phase 2 contraction of the pulmonary arterial hypoxic response depends on glycolytic ATP production but not on oxidative ATP production. These results indicate that the pulmonary vein and artery preferentially utilize different sources of energy for hypoxic contractions.
authors.affiliation: Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: C S
authors.initials: CS
authors.lastname: Packer
authors.forename: R A
authors.initials: RA
authors.lastname: Rhoades
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D010085:Oxidative Phosphorylation; D011651:Pulmonary Artery / Q000378:metabolism*; D011667:Pulmonary Veins / Q000378:metabolism*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose