|Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring.|
|PMID: 16914429 Owner: NLM Status: MEDLINE|
|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.|
|Denise S Fernandez-Twinn; Sofia Ekizoglou; Adrian Wayman; Clive J Petry; Susan E Ozanne|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-02-16|
|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|
|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|
|Languages: eng Pagination: R429-36 Citation Subset: IM|
|Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
Arrestins / metabolism
Blood Pressure / drug effects
Epinephrine / metabolism*
G-Protein-Coupled Receptor Kinase 3
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Heart / physiopathology*
Heart Rate / drug effects
Infant, Low Birth Weight / metabolism*, physiology
Isoproterenol / pharmacology
Maternal Nutritional Physiological Phenomena
Myocardium / metabolism
Prenatal Exposure Delayed Effects*
Receptors, Adrenergic, beta / metabolism*
beta-Adrenergic Receptor Kinases / metabolism
|AG-20608-02/AG/NIA NIH HHS|
|0/Arrestins; 0/Receptors, Adrenergic, beta; 0/beta-arrestin; 51-43-4/Epinephrine; 7683-59-2/Isoproterenol; EC 22.214.171.124/ADRBK2 protein, human; EC 126.96.36.199/Adrbk2 protein, rat; EC 188.8.131.52/G-Protein-Coupled Receptor Kinase 3; EC 184.108.40.206/beta-Adrenergic Receptor Kinases; EC 220.127.116.11/GTP-Binding Protein alpha Subunits, Gi-Go; EC 18.104.22.168/Adenylate Cyclase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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