Locus of hypoxic vasoconstriction in isolated ferret lungs

To determine whether hypoxic pulmonary vasoconstriction (HPV) occurs mainly in alveolar or extra-alveolar vessels in ferrets, we used two groups of isolated lungs perfused with autologous blood and a constant left atrial pressure (-5 Torr). In the first group, flow (Q̇) was held constant at 50, 100, and 150 ml·kg^-1·min^-1, and changes in pulmonary arterial pressure (Ppa) were recorded as alveolar pressure (Palv) was lowered from 25 to 0 Torr during control [inspired partial pressure of O₂ (PI(O₂) = 200 Torr] and hypoxic (PI(O₂) = 25 Torr) conditions. From these data, pressure-flow relationships were constructed at several levels of Palv. In the control state, lung inflation did not affect the slope of the pressure-flow relationships (ΔPpa/ΔQ̇), but caused the extrapolated pressure-axis intercept (Ppa₀), representing the mean backpressure to flow, to increase when Palv was ≥5 Torr. Hypoxia increased ΔPpa/ΔQ̇ and Ppa₀ at all levels of Palv. In contrast to its effects under control conditions, lung inflation during hypoxia caused a progressive decrease in ΔPpa/ΔQ̇, and did not alter Ppa₀ until Palv was ≥10 Torr. In the second group of experiments flow was maintained at 100 ml·kg^-1·min^-1, and changes in lung blood volume (LBV) were recorded as Palv was varied between 20 and 0 Torr. In the control state, inflation increased LBV over the entire range of Palv. In the hypoxic state inflation decreased LBV until Palv reached 8 Torr; at Palv 8-20 Torr, inflation increased LBV. The differences between the effects of inflation on the Ppa-Q̇ relationships and LBV in the control and hypoxic states suggest that in this preparation hypoxia caused constriction mainly in extra-alveolar vessels. Since similar previous studies in isolated pig lungs indicated that HPV occurred mainly in alveolar vessels, these results suggest that the site of HPV varies among species.