Document Detail


Ace gene dosage influences the development of renovascular hypertension.
MedLine Citation:
PMID:  19930431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Clinical and experimental evidence highlights the importance of the renin-angiotensin system in renovascular hypertension. Furthermore, genetic factors affecting angiotensin-converting enzyme (ACE) could influence the development of renovascular hypertension. 2. To test the effect of small gene perturbations on the development of renovascular hypertension, mice harbouring two or three copies of the Ace gene were submitted to 4 weeks of two-kidney, one-clip (2K1C) hypertension. Blood pressure (BP), cardiac hypertrophy, baroreflex sensitivity and blood pressure and heart rate variability were assessed and compared between the different groups. 3. The increase in BP induced by 2K1C was higher in mice with three copies of the Ace gene compared with mice with only two copies (46 vs 23 mmHg, respectively). Moreover, there was a 3.8-fold increase in the slope of the left ventricle mass/BP relationship in mice with three copies of the Ace gene. Micewith three copies of the Ace gene exhibited greater increases in cardiac and serum ACE activity than mice with only two copies of the gene. Both baroreflex bradycardia and tachycardia were significantly depressed in mice with three copies of the Ace gene after induction of 2K1C hypertension. The variance in basal systolic BP was greater in mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two copies of the gene (106 vs 54%, respectively). In addition, the low-frequency component of the pulse interval was higher mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two (168 vs 86%, respectively). Finally, in mice with three copies of the Ace gene, renovascular hypertension induced a 6.1-fold increase in the sympathovagal balance compared with a 3.2-fold increase in mice with only two copies of the gene. 4. Collectively, these data provide direct evidence that small genetic disturbances in ACE levels per se have an influence on haemodynamic, cardiac mass and autonomic nervous system responses in mice under pathological perturbation.
Authors:
Alexandre Ceroni; Edson D Moreira; Cristiano T Mostarda; Gustavo J J Silva; Eduardo M Krieger; Maria C Irigoyen
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-23
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  37     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  490-5     Citation Subset:  IM    
Affiliation:
Institute of Biomedical Science (ICB), Medical School, University of São Paulo, São Paulo, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Arrhythmias, Cardiac / genetics
Autonomic Nervous System / physiopathology
Baroreflex / genetics
Blood Pressure / genetics
Gene Dosage*
Genetic Association Studies
Genetic Predisposition to Disease*
Heart / physiopathology
Hemodynamics / genetics
Hypertension, Renovascular / blood,  genetics*,  metabolism,  physiopathology
Hypertrophy, Left Ventricular / genetics
Lung / enzymology
Male
Mice
Myocardium / enzymology
Peptidyl-Dipeptidase A / blood,  genetics*,  metabolism
Severity of Illness Index
Sympathetic Nervous System / physiopathology
Vagus Nerve / physiopathology
Chemical
Reg. No./Substance:
EC 3.4.15.1/Peptidyl-Dipeptidase A

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