doi: 10.1161/hh1201.093167
© 2001 American Heart Association, Inc.
Editorial |
Hypoxic Pulmonary Vasoconstriction
A Radical View
From the Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Md.
Correspondence to J.T. Sylvester, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail jsylv@welchlink.welch.jhu.edu
Key Words: KeyWords • hypoxia • vasoconstriction • vascular smooth muscle • reactive oxygen species • mitochondria
In 1894, when Bradford and Dean1 reported that asphyxia caused pulmonary hypertension, no one paid much attention. But ever since 1946, when von Euler and Liljestrand2 reported that acute hypoxia increased pulmonary arterial pressure attributable to pulmonary vasoconstriction, investigators have been hard at work to determine the underlying mechanisms. They have kept at it for more than half a century because of the important roles hypoxic pulmonary vasoconstriction (HPV) plays in health and disease.
Early work on HPV was performed almost exclusively in intact animals or isolated lungs. These preparations provided reproducible relevant responses, but their complexity placed limits on mechanistic investigation. The last decade has seen accelerated use of more reduced preparations, such as isolated vessels and vascular cells. These preparations provide more investigative precision, but relevance is sometimes uncertain, and special conditions are often necessary to achieve adequate reproducibility. Because of these problems, the mechanisms of HPV remain unknown, and a rapidly growing mass of inconsistent data has generated confusion and frustration, leading one investigator to title his symposium on HPV, "Can everyone be right?" and another investigator to title his review, "Can anyone be right?" Nevertheless, areas of tentative consensus are emerging.3
The primary mechanisms of HPV are contained entirely within
pulmonary vascular tissue. The main locus of the response is
small distal pulmonary arteries. The smooth muscle effector
pathway depends on an increase in cytoplasmic calcium concentration
([Ca2+]c) caused by
influx of calcium from extracellular fluid. Voltage-gated calcium
channels provide a major influx pathway;
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