Regulation of pulmonary circulation by alveolar oxygen tension via airway nitric oxide

Hiroshi Ide, Hitoshi Nakano, Toshiyuki Ogasa, Shinobu Osanai, Kenjirou Kikuchi, Jun Iwamoto
1999 Journal of applied physiology  
Regulation of pulmonary circulation by alveolar oxygen tension via airway nitric oxide. J. Appl. Physiol. 87(5): [1629][1630][1631][1632][1633][1634][1635][1636] 1999.-The effects of airway (AH) and vascular hypoxia (VH) on the production of nitric oxide (NO; V NO) 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
more » ... limb to the pulmonary artery. We measured exhaled NO (V NO), accumulation of perfusate NOx, and pulmonary arterial pressure (Ppa) during AH (inspired O 2 fraction ϭ 0.01) and/or VH (venous PO 2 ϭ 26 Torr). In BFL, a pure AH without VH caused decreases in V NO and NOx accumulation with a rise in Ppa. However, neither V NO, NOx accumulation, nor Ppa changed during VH. Similarly, in BLL, only AH reduced V NO, 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 V NO curvilinearly from 73.9 Ϯ 8 to 25.6 Ϯ 8 nl/min in BFL and from 26.0 Ϯ 2 to 5.2 Ϯ 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 µM for BLL and 24.1 µM for BFL. These results indicate that the V NO 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. hypoxia; epithelium; oxygen AN IMPORTANT FUNCTION of the lung is to match local perfusion with ventilation to preserve arterial oxygenation. Blood perfusion in the lung is redistributed according to alveolar ventilation; the PO 2 of the alveolus is, therefore, a major determinant of local blood flow. Such a mechanism has been described as hypoxic pulmonary vasoconstriction (HPV) (37). The main site of vasoconstriction in response to hypoxia has been demonstrated to be precapillary pulmonary arteries, and the primary stimulus for HPV is low alveolar PO 2 (PA O 2 ), whereas low PO 2 in mixed venous blood is only a weak stimulus (6, 35). A comparison of airway (AH) and vascular hypoxia (VH) was attempted in isolated animal lungs, and it demonstrated that AH had a greater effect on HPV (20, 39). HPV can be produced by direct 8750-7587/99 $5.00
doi:10.1152/jappl.1999.87.5.1629 pmid:10562601 fatcat:ldby2h7brjavdieeudzxppvray