Alterations in cardiac β-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs

Tai-Hwang Fan, Chang seng Liang, Seinosuke Kawashima, Shailesh P. Banerjee

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Abstract

The effects of congestive heart failure on the physiological and biochemical functions of the cardiac β-adrenoceptor-coupled adenylate cyclase system were studied in dogs with right heart failure produced by progressive pulmonary artery constriction and tricuspid avulsion. The cardiac inotropic response to dobutamine was attenuated in congestive heart failure, as determined by the right and left ventricular dP/dt responses. Adrenergic β-receptor density, measured by [3H]dihydroalprenolol binding, was reduced in membrane fractions of the failing right ventricle, but not in the left ventricle. The functional activity of the adenylate cyclase system was studied in vitro by measuring the net cyclic AMP production following additions of isoproterenol, 5'-guanylylimidodiphosphate (Gpp(NH)p), forskolin, or manganese chloride, which act either directly on the β-adrenergic receptors or on one of the post-receptor components of the adenylate cyclase system. Congestive heart failure reduced the net production of cyclic AMP by isoproterenol, Gpp(NH)p, and forskolin in both the right and left ventricles, but did not alter the effect of manganese chloride. Thus, β-receptor down-regulation is chamber-specific, occuring only in the hemodynamically stressed right ventricle. In contrast, the post-receptor defect of the adenylate cyclase system occured in both ventricles of the heart failure dogs. This decreased activation of adenylate cyclase by β-agonists may be responsible, at least in part, for the diminished cardiac inotropic response to catecholamines in congestive heart failure.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalEuropean Journal of Pharmacology
Volume140
Issue number2
DOIs
StatePublished - Aug 11 1987

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Adenylyl Cyclases
Adrenergic Receptors
Heart Failure
Heart Ventricles
Dogs
Guanylyl Imidodiphosphate
Colforsin
Isoproterenol
Cyclic AMP
Dihydroalprenolol
Dobutamine
Constriction
Pulmonary Artery
Catecholamines
Down-Regulation
Membranes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Alterations in cardiac β-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs. / Fan, Tai-Hwang; Liang, Chang seng; Kawashima, Seinosuke; Banerjee, Shailesh P.

In: European Journal of Pharmacology, Vol. 140, No. 2, 11.08.1987, p. 123-132.

Research output: Contribution to journalArticle

Fan, Tai-Hwang ; Liang, Chang seng ; Kawashima, Seinosuke ; Banerjee, Shailesh P. / Alterations in cardiac β-adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs. In: European Journal of Pharmacology. 1987 ; Vol. 140, No. 2. pp. 123-132.
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