In a canine model of heart failure, beta-adrenergic signaling abnormalities extend beyond receptor downregulation to include downstream impairments after cAMP production.
Post-receptor beta-adrenergic defects may blunt inotrope responses in HF; leaves open targeted downstream therapies pending human studies.
Although one of the salient abnormalities in signal transduction of failing myocardium is downregulation of the beta-adrenergic receptor, the extent of presentation of downstream pathways distal to beta-receptors is misunderstood. We addressed this question in tachypacing-induced canine failing heart by assessing changes in myofibrillar Ca2+ sensitivity and troponin I phosphorylation. At a basal state, no significant difference in myofibrillar Ca2+ sensitivity was found between normal and failing hearts. Isoproterenol 8-bromo-cylic adenosine monophosphate (cAMP), and 8-bromo-cAMP isobutylmethylxantine all significantly decreased the Ca2+ sensitivity in the normal, but not in the failing, heart. EMD57033 (10 microM ), a myofibrillar Ca2+ sensitizer increased the Ca2+ sensitivity to a similar extent in both groups. The troponin I phosphorylation levels were significantly decreased in the failing heart. These results suggest that abnormalities of the beta-adrenergic signaling system exist not only at the receptor level but also at downstream steps after cAMP production.
No takes yet. Share an insight, caveat, or question.
Satoh et al. (2002) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: