Authors
Zlatko I Pozeg, Evangelos D Michelakis, M Sean McMurtry, Bernard Thébaud, Xi-Chen Wu, Jason RB Dyck, Kyoko Hashimoto, Shaohua Wang, Rohit Moudgil, Gwyneth Harry, Richard Sultanian, Arvind Koshal, Stephen L Archer
Publication date
2003/4/22
Journal
Circulation
Volume
107
Issue
15
Pages
2037-2044
Publisher
Lippincott Williams & Wilkins
Description
Background— Alveolar hypoxia acutely elicits pulmonary vasoconstriction (HPV). Chronic hypoxia (CH), despite attenuating HPV, causes pulmonary hypertension (CH-PHT). HPV results, in part, from inhibition of O2-sensitive, voltage-gated potassium channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). CH decreases Kv channel current/expression and depolarizes and causes Ca2+ overload in PASMCs. We hypothesize that Kv gene transfer would normalize the pulmonary circulation (restore HPV and reduce CH-PHT), despite ongoing hypoxia.
Methods and Results— Adult male Sprague-Dawley rats were exposed to normoxia or CH for 3 to 4 weeks and then nebulized orotracheally with saline or adenovirus (Ad5) carrying genes for the reporter, green fluorescent protein reporter±human Kv1.5 (cloned from normal PA). HPV was assessed in isolated lungs. Hemodynamics, including Fick and …
Total citations
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