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(Hypertension. 1996;27:265-268.)
© 1996 American Heart Association, Inc.

Articles

Impaired Regulation of Cell Communication by ß-Adrenergic Receptor Activation in the Failing Heart

Walmor C. De Mello

From the Departments of Pharmacology and Anesthesiology, School of Medicine, University of Puerto Rico, San Juan.

Abstract We investigated the influence of ß-adrenergic receptor activation on the control of gap junctional conductance (gj) in the heart of cardiomyopathic hamsters (11 months old). We measured gj in isolated ventricular cell pairs using two voltage-clamp circuits. Administration of isoproterenol (10^-6 mol/L) to the bath had no effect on gj in myopathic cell pairs but increased gj by 45±3% (±SE) in normal hamsters. Moreover, forskolin (10^-7 mol/L), an activator of adenyl cyclase, did not change gj in myopathic cells but enhanced gj by 23±2.8% in controls. Similar results were obtained with isobutylmethylxanthine (10^-6 mol/L), a phosphodiesterase inhibitor. Dibutyryl-cAMP (10^-6 mol/L), however, increased gj of cardiomyopathic cell pairs by 58±2.1% within 2 minutes and enhanced gj in controls by 50±3.6%. The effect of dibutyryl-cAMP on gj of myopathic cells was suppressed by intracellular dialysis of an inhibitor of protein kinase A. These observations indicate that the regulation of gj by the ß-adrenergic receptor–G protein–adenyl cyclase signaling system is greatly impaired in the failing heart but the ability of cAMP to increase gj is still preserved.

Key Words: receptors, adrenergic, beta activation • gap junctions • heart

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