doi: 10.1161/01.RES.00000175934.68087.29
© 2005 American Heart Association, Inc.
Editorials |
Vascular Remodeling Versus Vasoconstriction in Chronic Hypoxic Pulmonary Hypertension
A Time for Reappraisal?
From the University of Colorado Health Sciences Center, Developmental Lung Biology Laboratory (K.R.S.) and Cardiovascular Pulmonary Research Laboratory (I.F.M.), Denver, Colo.
Correspondence to Dr Kurt R. Stenmark, Professor of Pediatrics, University of Colorado Health Sciences Center, 4200 E. 9th Ave, Box B131, Denver, CO 80262. E-mail Kurt.Stenmark@UCHSC.edu
See related article, pages 185–191
Key Words: pulmonary hypertension • hypoxia • vascular remodeling • Rho kinase • angiogenesis
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Chronic or sustained pulmonary hypertension is a complication of residence at high altitudes and chronic lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, asthma, and sleep apnea. Alveolar hypoxia is an important (though probably not exclusive) contributor to the pulmonary hypertension observed in these conditions. Further, it is widely accepted that secondary hypoxic pulmonary hypertension is strongly associated with increased morbidity and reduced survival.1,2 These facts have led to intense research efforts to identify the underlying mechanisms contributing to this condition, with the ultimate goal of identifying and developing novel therapeutic interventions. This work has relied heavily on the use of animal models, and one of the most commonly used is exposure of rats to chronic-hypoxic conditions by nitrogen dilution or hypobaria. Observations, predominately in this model, have led to the longstanding and widely accepted theory that chronic hypoxic pulmonary hypertension results from a combination of sustained vasoconstriction and vascular remodeling. It is generally believed that the contribution of vasoconstriction is greatest early in the disease process and that structural remodeling of the pulmonary vascular bed becomes progressively more important over time. That structural change is an important determinant of increased resistance and pressure in chronic pulmonary hypertension is supported by observations that over time of exposure to hypoxia, acute reexposure to normal or even high levels of inspired oxygen becomes progressively less effective in reducing the pulmonary arterial pressure. This lack of responsiveness to oxygen, or even to other pulmonary vasodilators such as Ca2+ channel blockers,
Related Article:
Circ. Res. 2005 97: 185-191.
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