Document Detail

Targeted disruption of the gene for natriuretic peptide receptor-A worsens hypoxia-induced cardiac hypertrophy.
MedLine Citation:
PMID:  11748047     Owner:  NLM     Status:  MEDLINE    
Targeted disruption of the gene for natriuretic peptide receptor-A (NPR-A) worsens pulmonary hypertension and right ventricular hypertrophy during hypoxia, but its effect on left ventricular mass and systemic pressures is not known. We examined the effect of 3 wk of hypobaric hypoxia (0.5 atm) on right and left ventricular pressure and mass in mice with 2 (wild type), 1, or 0 copies of Npr1, the gene that encodes for NPR-A in mice. Under normoxic conditions, right ventricular peak pressure (RVPP) was greater in 0 than in 2 copy mice, but there were no genotype-related differences in carotid artery PP (CAPP). The left ventricular free wall weight-to-body weight (LV/body wt) ratio was greater in 0 than in 2 copy mice and there was a trend toward a greater right ventricular weight-to-body weight (RV/body wt) ratio. Three weeks of hypoxia increased RVPP and RV/body wt in all genotypes. The increase in RVPP was similar in all genotypes (11-14 mmHg), but the hypoxia-induced increase in RV/body wt was more than twice as great in 0 copy mice than in 2 copy mice (1.11 +/- 0.06 to 2.65 +/- 0.46 vs. 0.96 +/- 0.04 to 1.4 +/- 0.09, P < 0.05). Chronic hypoxia had no effect on CAPP in any genotype and did not effect LV/body wt in 1 or 2 copy mice, but increased LV/body wt 41% in 0 copy mice. We conclude that absent expression of NPR-A worsens right ventricular hypertrophy and causes left ventricular hypertrophy during exposure to chronic hypoxia without increasing pulmonary or systemic arterial pressure responses.
James R Klinger; Rod R Warburton; Linda Pietras; Paula Oliver; Jennifer Fox; Oliver Smithies; Nicholas S Hill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  282     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-18     Completed Date:  2002-01-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H58-65     Citation Subset:  IM    
Division of Pulmonary, Sleep, and Critical Care Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, RI 02903, USA.
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MeSH Terms
Anoxia / complications,  physiopathology*
Atrial Natriuretic Factor / blood
Cardiomegaly / etiology,  physiopathology*
Carotid Arteries / physiopathology
Disease Progression
Guanylate Cyclase / deficiency,  genetics,  physiology*
Hydroxyproline / analysis
Lung / pathology
Mice, Knockout
Pulmonary Circulation / physiology
Receptors, Atrial Natriuretic Factor / deficiency,  genetics,  physiology*
Ventricular Function, Left / physiology
Ventricular Function, Right / physiology
Grant Support
Reg. No./Substance:
51-35-4/Hydroxyproline; 85637-73-6/Atrial Natriuretic Factor; EC Cyclase; EC, Atrial Natriuretic Factor; EC natriuretic factor receptor A

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