MINIREVIEW
Altered Pulmonary Vasoreactivity in the Chronically Hypoxic Lung
L. A. Shimoda, J. S. K. Sham, J. T. Sylvester
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University,
School of Medicine Baltimore, Maryland, USA
Received February 29, 2000
Accepted April 3, 2000
Summary
Prolonged exposure to alveolar hypoxia induces physiological
changes in the pulmonary vasculature that result in the development of pulmonary
hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in
vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is
influenced by vasoconstrictor and vasodilator factors secreted from the
endothelium, lung parenchyma and in the circulation. During chronic hypoxia,
production of vasoconstrictors such as endothelin-1and angiotensin II is
enhanced locally in the lung, while synthesis of vasodilators may be reduced.
Altered reactivity to these vasoactive agonists is another physiological
consequence of chronic exposure to hypoxia. Enhanced contraction in response to
endothelin-1 and angiotensin II, as well as depressed vasodilation in response
to endothelium-derived vasodilators, has been documented in models of hypoxic
pulmonary hypertension. Chronic hypoxia may also have direct effects on
pulmonary vascular smooth muscle cells, modulating receptor population, ion
channel activity or signal transduction pathways. Following prolonged hypoxic
exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current,
membrane depolarization, elevation in resting cytosolic calcium and changes in
signal transduction pathways. These changes in the electrophysiological
parameters of pulmonary vascular smooth muscle cells are likely associated with
an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary
arterial myocyte function, changes in synthesis of vasoactive factors and
altered vasoresponsiveness to these agents may shift the environment in the lung
to one of contraction instead of relaxation, resulting in increased pulmonary
vascular resistance and elevated pulmonary arterial pressure.
Key words
Contraction · Endothelin-1 · Angiotensin II · Nitric oxide ·
Membrane potential · Pulmonary hypertension
Reprint requests
Larissa A. Shimoda, Ph.D., Division of Pulmonary and Critical
Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA, FAX
(410)-550-2612, E-mail: shimodal@welch.jhu.edu
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