Response of Failing Canine and Human Heart Cells to β 2 -Adrenergic Stimulation
| Autor: | Larry R. Jones, George E. Billman, J. Hensley, Ruth A. Altschuld, Edward G. Lakatta, Rui-Ping Xiao, Richard H. Fertel, Pierre Marie L. Robitaille, C. M. Hohl, Robert L. Hamlin, L. C. Castillo, Randall C. Starling |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty medicine.drug_class Stimulation Propanolamines chemistry.chemical_compound Dogs Physiology (medical) Internal medicine Cyclic AMP medicine Carnivora Animals Humans Myocyte Phosphorylation Zinterol Receptor Aged Heart Failure Voltage-dependent calcium channel business.industry Calcium-Binding Proteins Isoproterenol Heart Adrenergic beta-Agonists Middle Aged medicine.disease Endocrinology chemistry Ethanolamines Heart failure Female Receptors Adrenergic beta-2 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 92:1612-1618 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.92.6.1612 |
| Popis: | Background Failing human hearts lose β 1 - but not β 2 -adrenergic receptors. In canine hearts with tachypacing failure, the ratio of β 2 - to β 1 -adrenergic receptors is increased. The present study was designed to determine whether heart failure increases sensitivity to β 2 -adrenergic stimulation in isolated canine ventricular cardiomyocytes and to verify that myocytes from failing human ventricles contain functional β 2 -adrenergic receptors. Methods and Results Myocytes from healthy dogs, dogs with tachypacing failure, and human transplant recipients were loaded with fura 2-AM and subjected to electric field stimulation in the presence of zinterol, a highly selective β 2 -adrenergic agonist. Zinterol significantly increased [Ca 2+ ] i transient amplitudes in all three groups. The failing canine myocytes were significantly more responsive than normal to β 2 -adrenergic stimulation. We also measured isotonic twitches, indo-1 fluorescence transients, and L-type Ca 2+ currents in healthy canine myocytes. Zinterol (10 −5 mol/L) elicited large increases in the amplitudes of simultaneously recorded twitches and [Ca 2+ ] i transients. Zinterol also increased L-type Ca 2+ currents in the normal canine myocytes; this augmentation was abolished by 10 −7 mol/L ICI 118,551. cAMP production by suspensions of healthy and failing canine myocytes was not increased by zinterol (10 −9 to 10 −5 mol/L), nor did 10 −5 mol/L zinterol elicit phospholamban phosphorylation. Conclusions Failing human ventricular cardiomyocytes contain functional β 2 -adrenergic receptors. Canine myocytes also contain functional β 2 -adrenergic receptors. The canine ventricular response to β 2 -agonists is increased in tachypacing failure. Positive inotropic responses to β 2 -stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban. |
| Databáze: | OpenAIRE |
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