Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats

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Abstract
The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 rnmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was <1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia. The inflection point and negative preinflection slope, however, indicate that there is also extra-alveolar muscular tone in chronically hypoxic rats both during normoxia and hypoxia. The results have implications for the hypoxic human lung, whose anatomy resembles that of the hypoxic rat.