Document Detail

Intermittent hypoxia induces early functional cardiovascular remodeling in mice.
MedLine Citation:
PMID:  17962641     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Intermittent hypoxia, a hallmark of sleep apnea, is a major factor for hypertension and impaired vasoreactivity. OBJECTIVES: To examine the temporal occurrence of these two outcomes in order to provide insight into mechanisms and early cardiovascular disease identification. METHODS: Functional and structural cardiovascular alterations were assessed in C57BL6 mice exposed to intermittent hypoxia (21-4% Fi(O(2)), 30-s cycle, 8 h/d) or air for up to 35 days. Blood pressure, heart rate, and urinary catecholamines were measured at Days 1 and 14. Hindquarter vasoreactivity was assessed at Days 14 and 35, including vasoconstriction to norepinephrine, endothelium-, and non-endothelium-dependent vasodilation. Aorta, heart, and hindquarter skeletal muscles were immunostained for vascular markers PECAM-1 and collagen IV. MEASUREMENTS AND MAIN RESULTS: Hemodynamic alterations occurred from Day 1, characterized by blood pressure surges with bradytachyarrhythmia driven by cyclic hypoxia. At Day 14, blood pressure at normoxia was elevated, with predominant diastolic increase. With hypoxia, vasopressive catecholamines were elevated, blood pressure surged with a lower hypoxic threshold, whereas heart rate fluctuations decreased. Histologic alterations started from Day 14, with decreased endothelial PECAM-1 expression in descending aorta and left heart. Impaired peripheral vasoreactivity occurred at Day 35, including hypervasoconstriction to norepinephrine secondary to sympathetic hyperactivity, without changes in pre- and postsynaptic alpha-adrenoceptors or in endothelium- and non-endothelium-dependent vasodilation. CONCLUSIONS: Intermittent hypoxia induces sequential cardiovascular events suggesting increased chemoreflex and depressed baroreflex, resulting in sympathoadrenal hyperactivity, early hemodynamic alterations with proximal histologic remodeling, and delayed changes in peripheral vasoreactivity. Such early alterations before overt cardiovascular disease strengthen the need for identifying at-risk individuals for systematic treatment.
Maurice Dematteis; Cécile Julien; Christiane Guillermet; Nathalie Sturm; Sylvie Lantuejoul; Michel Mallaret; Patrick Lévy; Evelyne Gozal
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-25
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  177     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-31     Completed Date:  2008-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  227-35     Citation Subset:  AIM; IM    
Laboratoire HP2, Institut Jean Roget, Faculté de Médecine de Grenoble, 38042 Grenoble Cedex 09, France.
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MeSH Terms
Acetylcholine / pharmacology
Anoxia / pathology,  physiopathology*
Blood Pressure
Catecholamines / blood
Disease Models, Animal
Heart Rate
Mice, Inbred C57BL
Myocardium / pathology
Sleep Apnea Syndromes / physiopathology*
Transforming Growth Factor beta1 / blood
Vasoconstriction / drug effects
Ventricular Remodeling*
Reg. No./Substance:
0/Catecholamines; 0/Transforming Growth Factor beta1; 51-84-3/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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