Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction

Weerackody, R. P., Welsh, D. J., Wadsworth, R. M. and Peacock, A. J. (2009) Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction. American Journal of Physiology: Heart and Circulatory Physiology, 296(5), H1312-H1320. (doi: 10.1152/ajpheart.00977.2008)

Abstract

Weerackody RP, Welsh DJ, Wadsworth RM, Peacock AJ. Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction. Am J Physiol Heart Circ Physiol 296: H1312-H1320, 2009. First published February 6, 2009; doi:10.1152/ajpheart.00977.2008.-Hypoxia-induced endothelial dysfunction plays a crucial role in the pathogenesis of hypoxic pulmonary hypertension. p38 MAPK expression is increased in the pulmonary artery following hypoxic exposure. Recent evidence suggests that increased p38 MAPK activity is associated with endothelial dysfunction. However, the role of p38 MAPK activation in pulmonary artery endothelial dysfunction is not known. Sprague-Dawley rats were exposed to 2 wk hypobaric hypoxia, which resulted in the development of pulmonary hypertension and vascular remodeling. Endothelium-dependent relaxation of intrapulmonary vessels from hypoxic animals was impaired due to a reduced nitric oxide (NO) generation. This was despite increased endothelial NO synthase immunostaining and protein expression. Hypoxia exposure increased superoxide generation and p38 MAPK expression. The inhibition of p38 MAPK restored endothelium-dependent relaxation, increased bioavailable NO, and reduced superoxide production. In conclusion, the pharmacological inhibition of p38 MAPK was effective in increasing NO generation, reducing superoxide burden, and restoring hypoxia-induced endothelial dysfunction in rats with hypoxia-induced pulmonary hypertension. p38 MAPK may be a novel target for the treatment of pulmonary hypertension.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Welsh, Dr David and Peacock, Professor Andrew
• Authors: Weerackody, R. P., Welsh, D. J., Wadsworth, R. M., and Peacock, A. J.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Physiology: Heart and Circulatory Physiology
• Publisher: American Physiological Society
• ISSN: 0363-6135
• ISSN (Online): 1522-1539