Myocardial β-adrenergic receptor function during the development of pacing-induced heart failure

K. Kiuchi, R. P. Shannon, K. Komamura, D. J. Cohen, C. Bianchi, C. J. Homcy, S. F. Vatner, D. E. Vatner

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

The development of pacing-induced heart failure was studied in chronically instrumented, conscious dogs paced at a rate of 240 beats/min for 1 d (n = 6), 1 wk (n = 6), and 3-4 wk (n = 7). Left ventricular (LV) dP/dt was decreased (P < 0.0125) at 1 d, LV end-diastolic pressure and heart rate were increased (P < 0.0125) at 1 wk, but clinical signs of heart failure were only observed after 3-4 wk of pacing. Plasma norepinephrine rose (P < 0.0125) after 1 d of pacing, whereas LV norepinephrine was reduced (P < 0.0125) only after 3-4 wk of pacing. Both the fraction of β-adrenergic receptors binding agonist with high affinity and adenylyl cyclase activity decreased (P < 0.0125) after 1 d of pacing. Total β-adrenergic receptor density was not changed at any time point, but β1-adrenergic receptor density was decreased (P < 0.0125) after 1 wk. The functional activity of the guanine nucleotide binding protein, G(s), was not reduced, but the G(iα2) isoform of the α subunit of the GTP-inhibitory protein rose after 3-4 wk of pacing. Thus, myocardial β-adrenergic signal transduction undergoes change shortly (1 d) after the initiation of pacing, before heart failure develops. The mechanism of β-adrenergic receptor dysfunction in pacing-induced heart failure is characterized initially by elevated plasma levels of catecholamines, uncoupling of β-adrenergic receptors, and a defect in the adenylyl cyclase catalytic unit. Selective down-regulation of β-adrenergic receptors, increases in G(iα2), and decreases in myocardial catecholamine levels occur as later events.

Original languageEnglish (US)
Pages (from-to)907-914
Number of pages8
JournalJournal of Clinical Investigation
Volume91
Issue number3
DOIs
StatePublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Keywords

  • adenylyl cyclase
  • congestive heart failure
  • norepinephrine
  • β-adrenergic receptors
  • β-adrenergic receptors

Fingerprint

Dive into the research topics of 'Myocardial β-adrenergic receptor function during the development of pacing-induced heart failure'. Together they form a unique fingerprint.

Cite this