Document Detail


Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring.
MedLine Citation:
PMID:  16914429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Low birth weight in humans is associated with an increased risk of cardiovascular disease. Humans with heart failure have a reduced beta-adrenergic response. The aim of this study was to investigate the hemodynamic response to the beta-adrenergic agonist isoproterenol and to identify molecular deficiencies that may be predictive of cardiac failure in a low-birth weight rodent model that develops insulin resistance and type 2 diabetes in adulthood. Wistar rats were fed a control or a low-protein (LP) diet throughout pregnancy and lactation. The resting heart rate and blood pressure of the 3-mo-old male offspring of these dams, termed "control" and "LP" groups, respectively, and their responses to isoproterenol (ISO) infusion were monitored by radiotelemetry. The protein expression of beta-adrenergic signaling components was also measured by Western blot analysis. Basal heart rate was increased in LP offspring (P<0.04), although mean arterial pressure was comparable with controls. Chronotropic effects of ISO were blunted in LP offspring with significant delays to maximal response (P=0.01), a shorter duration of response (P=0.03), and a delayed return to baseline (P=0.01) at the lower dose (0.1 microg.kg-1.min-1). At the higher dose (1.0 microg.kg-1.min-1 ISO), inotropic response was blunted (P=0.03) but quicker (P=0.001). In heart tissue of LP offspring, beta1-adrenergic receptor expression was reduced (P<0.03). beta1-Adrenergic receptor kinase and both stimulatory and inhibitory G protein levels remained unchanged, whereas beta-arrestin levels were higher (P<0.03). Finally, insulin receptor-beta expression was reduced in LP offspring (P<0.012). LP offspring have reduced beta-adrenergic responsiveness and attenuated adrenergic and insulin signaling, suggesting that intrauterine undernutrition alters heart failure risk.
Authors:
Denise S Fernandez-Twinn; Sofia Ekizoglou; Adrian Wayman; Clive J Petry; Susan E Ozanne
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-02-16
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  291     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-17     Completed Date:  2006-09-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R429-36     Citation Subset:  IM    
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK. df220@cam.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Arrestins / metabolism
Blood Pressure / drug effects
Diet, Protein-Restricted
Epinephrine / metabolism*
Female
G-Protein-Coupled Receptor Kinase 3
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Heart / physiopathology*
Heart Rate / drug effects
Humans
Infant, Low Birth Weight / metabolism*,  physiology
Infant, Newborn
Isoproterenol / pharmacology
Male
Maternal Nutritional Physiological Phenomena
Models, Animal
Myocardium / metabolism
Pregnancy
Prenatal Exposure Delayed Effects*
Rats
Rats, Wistar
Receptors, Adrenergic, beta / metabolism*
Signal Transduction
beta-Adrenergic Receptor Kinases / metabolism
Grant Support
ID/Acronym/Agency:
AG-20608-02/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Arrestins; 0/Receptors, Adrenergic, beta; 0/beta-arrestin; 51-43-4/Epinephrine; 7683-59-2/Isoproterenol; EC 2.7.11.15/ADRBK2 protein, human; EC 2.7.11.15/Adrbk2 protein, rat; EC 2.7.11.15/G-Protein-Coupled Receptor Kinase 3; EC 2.7.11.15/beta-Adrenergic Receptor Kinases; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go; EC 4.6.1.1/Adenylate Cyclase

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


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