Document Detail

NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction of isolated rabbit lungs.
MedLine Citation:
PMID:  11238003     Owner:  NLM     Status:  MEDLINE    
Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation but may also result in chronic pulmonary hypertension. It has not been clarified whether acute HPV and the response to prolonged alveolar hypoxia are triggered by identical mechanisms. We characterized the vascular response to sustained hypoxic ventilation (3% O(2) for 120-180 min) in isolated rabbit lungs. Hypoxia provoked a biphasic increase in pulmonary arterial pressure (PAP). Persistent PAP elevation was observed after termination of hypoxia. Total blockage of lung nitric oxide (NO) formation by N(G)-monomethyl-L-arginine caused a two- to threefold amplification of acute HPV, the sustained pressor response, and the loss of posthypoxic relaxation. This amplification was only moderate when NO formation was partially blocked by the inducible NO synthase inhibitor S-methylisothiourea. The superoxide scavenger nitro blue tetrazolium and the superoxide dismutase inhibitor triethylenetetramine reduced the initial vasoconstrictor response, the prolonged PAP increase, and the loss of posthypoxic vasorelaxation to a similar extent. The NAD(P)H oxidase inhibitor diphenyleneiodonium nearly fully blocked the late vascular responses to hypoxia in a dose that effected a decrease to half of the acute HPV. In conclusion, as similarly suggested for acute HPV, lung NO synthesis and the superoxide-hydrogen peroxide axis appear to be implicated in the prolonged pressor response and the posthypoxic loss of vasorelaxation in perfused rabbit lungs undergoing 2-3 h of hypoxic ventilation.
N Weissmann; S Winterhalder; M Nollen; R Voswinckel; K Quanz; H A Ghofrani; R T Schermuly; W Seeger; F Grimminger
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  280     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-12     Completed Date:  2001-04-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L638-45     Citation Subset:  IM    
Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, 35392 Giessen, Germany.
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MeSH Terms
Anoxia / physiopathology*
Blood Pressure
Nitric Oxide / physiology*
Pulmonary Artery / physiopathology
Pulmonary Circulation*
Reactive Oxygen Species / physiology*
Vasoconstriction / physiology*
Reg. No./Substance:
0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide

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