Hypoxia on the pulmonary circulation: how and where it acts

Abstract

Thirty years have elapsed since von Euler and Liljestrand advanced the proposition that acute hypoxia elicits pulmonary vasoconstriction. The idea was not new, but the report excited considerable interest because it was both propitious and prescient. Nineteen forty six was a good year to perceive that the pulmonary vasoconstrictor response to hypoxia is part of a self regulatory mechanism by which pulmonary capillary blood flow is automatically adjusted to alveolar ventilation: methods had been standardized for exploring the pulmonary circulation in a systematic and sophisticated way and the introduction of cardiac catheterization had bought the previously remote pulmonary circulation within reach. Much has been learned since then about the pulmonary circulation and the pressor response to acute hypoxia. Particularly helpful in dispelling the original misgivings about the occurrence of a pressor response to acute hypoxia has been a succession of observations on cattle in which the pulmonary pressor response to hypoxia is much greater than in the conventional laboratory animal, particularly in the postnatal period. That pulmonary vasoconstriction underlies the rise in pulmonary arterial pressure no longer is in doubt. The biological significance of this mechanism has been sought both in human disease and in animals. And, the lessons from acute hypoxia have been extended to the chronic hypoxia of high altitude which also has proved to be associated with pulmonary vasoconstriction. As uncertainty after uncertainty evaporated, two key questions came into sharp focus: By what mechanism(s) does hypoxia elicit vasoconstriction? What segment(s) of the pulmonary vascular tree constrict(s) during hypoxia? The purpose of this paper is to offer a view of the answers to these questions. And, after having proposed how and where acute hypoxia works, brief consideration will be given to the question of how the observations on acute hypoxia generally an artifice of the laboratory are related to the state of chronic hypoxia which characterizes life at high altitude.