Document Detail

Postnatal intermittent hypoxia and developmental programming of hypertension in spontaneously hypertensive rats: the role of reactive oxygen species and L-Ca2+ channels.
MedLine Citation:
PMID:  18474836     Owner:  NLM     Status:  MEDLINE    
Obstructive and central apneas during sleep are associated with chronic intermittent hypoxia (CIH) and increased cardiovascular morbidity. Spontaneously hypertensive rats exposed to CIH during postnatal days 4 to 30 develop exaggerated hypertension as adults. We hypothesized that reactive oxygen species and altered L-Ca(2+) channel activity may underlie the postnatal programming of exaggerated blood pressure and cardiac remodeling. Newborn male spontaneously hypertensive rats were exposed to CIH (10% and 21% O(2) alternating every 90 seconds, 12 h/d, for postnatal days 4 to 30) or normoxia (room air). In each condition, spontaneously hypertensive rats received daily (SC) 1 of 3 treatments: L-calcium channel blocker nifedipine (5 mg/kg), superoxide dismutase mimetic MnTMPyP pentachloride (10 mg/kg), or vehicle (polyethylene glycol). Blood pressure was evaluated monthly for 6 months after birth, and echocardiographic assessments were conducted at 6 months of age. CIH vehicle-treated rats presented higher systolic blood pressure (187+/-5 mm Hg) as compared with normoxic vehicle treated controls (163+/-2 mm Hg; P<0.001). Postnatal CIH elicited marked increases in left ventricular wall thickness in a pattern of concentric hypertrophy with augmented systolic contractility. The treatment with nifedipine in the CIH group attenuated blood pressure (159+/-2 mm Hg; P<0.001) and normalized left ventricular wall thickness and systolic function, whereas the treatment with SOD mimetic decreased blood pressure (165+/-2 mm Hg; P<0.001) and reduced left ventricular wall thickness without changes in the systolic function. We conclude that Ca(2+) and reactive oxygen species-mediated signaling during intermittent hypoxia are critical mechanisms underlying postnatal programming of an increased severity of hypertension and hypertrophic cardiac remodeling in a genetically susceptible rodent model.
Galia K Soukhova-O'Hare; Roger V Ortines; Yan Gu; Alexander D Nozdrachev; Sumanth D Prabhu; David Gozal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-12
Journal Detail:
Title:  Hypertension     Volume:  52     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-20     Completed Date:  2008-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  156-62     Citation Subset:  IM    
Kosair Children's Hospital Research Institute, University of Louisville, KY 40202, USA.
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MeSH Terms
Anoxia / complications*
Antioxidants / pharmacology
Blood Pressure / drug effects
Body Weight
Calcium Channel Blockers / pharmacology
Calcium Channels, L-Type / drug effects,  metabolism*
Heart Rate / drug effects
Heart Ventricles / drug effects,  physiopathology,  ultrasonography
Hypertension / etiology*,  metabolism*,  prevention & control
Lipid Peroxides / analysis
Metalloporphyrins / pharmacology
Nifedipine / pharmacology
Rats, Inbred SHR
Reactive Oxygen Species / metabolism*
Ventricular Remodeling / drug effects
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Lipid Peroxides; 0/Metalloporphyrins; 0/Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; 0/Reactive Oxygen Species; 21829-25-4/Nifedipine

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

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