title: Regulation of pulmonary circulation by alveolar oxygen tension via airway nitric oxide.
abstract: The effects of airway (AH) and vascular hypoxia (VH) on the production of nitric oxide (NO; VNO) were tested in isolated buffer-perfused (BFL) and blood-perfused rabbit lungs (BLL). To produce AH and/or VH, the lung was ventilated with 1% O(2) gas, and/or the perfusate was deoxygenated by a membrane oxygenator located on the inlet limb to the pulmonary artery. We measured exhaled NO (VNO), accumulation of perfusate NOx, and pulmonary arterial pressure (Ppa) during AH (inspired O(2) fraction = 0.01) and/or VH (venous PO(2) = 26 Torr). In BFL, a pure AH without VH caused decreases in VNO and NOx accumulation with a rise in Ppa. However, neither VNO, NOx accumulation, nor Ppa changed during VH. Similarly, in BLL, only AH reduced VNO, although NOx accumulation was not measurable because of Hb. When alveolar PO(2) was gradually reduced from 152 to 0 Torr for 20 min, AH reduced VNO curvilinearly from 73.9 +/- 8 to 25.6 +/- 8 nl/min in BFL and from 26.0 +/- 2 to 5. 2 +/- 1 nl/min in BLL. This plot was analogous to that of a substrate-velocity curve for an enzyme obeying Michaelis-Menten kinetics. The apparent Michaelis-Menten constant for O(2) was calculated to be 23.2 microM for BLL and 24.1 microM for BFL. These results indicate that the VNO in the airway epithelia is dependent on the level of inspired O(2) fraction, leading to the tentative conclusion that epithelial NO synthase is O(2) sensitive over the physiological range of alveolar PO(2) and controls pulmonary circulation.
authors.affiliation: Department of Medicine, School of Nursing, Asahikawa Medical College, Asahikawa 078-8510, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ide
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Ogasa
authors.forename: S
authors.initials: S
authors.lastname: Osanai
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: J
authors.initials: J
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D002021:Buffers; D004730:Endothelium, Vascular / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D002021:Buffers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III