Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring. 1691 29