Mechanisms of hypoxic pulmonary vasoconstriction

NF Voelkel - American Review of Respiratory Disease, 1986 - atsjournals.org
NF Voelkel
American Review of Respiratory Disease, 1986atsjournals.org
Introduction 1 he subject of hypoxic pulmonary vasoconstriction has attracted great interest
since its first description by von Euler and Liljestrand in 1946 (2). The elusive mechanisms of
alveolar hypoxia-induced constriction of lung vessels are still one of the vexing problems of
modern physiology and a continual challenge for those interested in the lung circulation.
Beyond the understanding of an important regulatory mechanism in the lung, the
investigators in the field hope to understand the process of oxygen sensing of tissues and …
Introduction
1 he subject of hypoxic pulmonary vasoconstriction has attracted great interest since its first description by von Euler and Liljestrand in 1946 (2). The elusive mechanisms of alveolar hypoxia-induced constriction of lung vessels are still one of the vexing problems of modern physiology and a continual challenge for those interested in the lung circulation. Beyond the understanding of an important regulatory mechanism in the lung, the investigators in the field hope to understand the process of oxygen sensing of tissues and how a decrease in the oxygen tension is translated into contractile action of muscles. After Motley and coworkers (3) demonstrated that breathing a gas mixture with low oxygen causes an increase in pulmonary arterial pressure in normal humans, the hypoxic pulmonary pressor response was studied in humans at altitude (4), in patients with obstructive lung disease (5)(table 1), in pregnancy (6), and during fetal (7-11) and newborn life (12, 13). The consensus is that hypoxic pulmonary vasoconstriction is an eminently important component in a control system that matches ventilation and per fusion and preserves arterial Po2. The guiding teleologic principle in the design of the lung must have been: what is not ventilated must not be perfused. This principle is evident in the fetal lung circulation: the collapsed airless lung has very little blood flow, an extreme of ventilation-perfusion (V/Q) regulation that can be encountered in the adult life in atelectatic lobes (14). Yet the pulmonary hypertension observed in some patients with global hypoxemia dif fers from this powerful fetal pulmonary vascular response, because the fetal vascular response is reversible with the first breath. This is likely due to structural vascular alterations that may be consequences of the disease or of chronic vasoconstriction or possibly of chronic hypoxia itself. These structural alterations of the chronically hypoxic vascular bed are not considered here and have been reviewed elsewhere (15-17).
Since Fishman's review (18), the introduction of micropuncture techniques and direct measurement of pressures in the lung microcirculation (19) mark the progress that has been made in answering the question of what segment (s) of the pulmonary vascular tree constrict (s) during hypoxia. The second key question raised in Fishman's important article—" By what mechanism (s) does hypoxia elicit vasoconstriction?"—has been the subject of more recent reviews (20-22) and of a Conference on Pulmonary Vascular Reactivity (23). The purpose of this review is to put recent clinical data and research results into perspective and to highlight and integrate current hypotheses.
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