Lidocaine increases the number of β-adrenoceptors in neonatal rat cardiocytes in culture

Abstract

Some physiological functions of the heart are modulated through cardiac β-adrenoceptors. In acute myocardial infarction, ventricular arrhythmias occur frequently and class I antiarrhythmic drugs such as lidocaine are often administered continuously over long period. The aim of this study was to investigate the effects of long-term treatment with lidocaine on cardiac β-adrenoceptors. Ventricular cardiocytes from 2-day-old Wistar rat were cultured in the presence or absence of lidocaine, and, β-adrenoceptors of the membrane fraction of the cells were measured with a binding assay using [¹²⁵I] -iodocyanopindolol ([¹²⁵I] CYP) as a radioligand. When the cells were cultured in the presence of lidocaine at clinical or toxic concentrations, the binding of [¹²⁵I]CYP to the cells increased in a concentration (10⁻⁵ mol/l-10⁻³ mol/l) — and time (12–72h) —dependent manner. The effect was due to an increase in maximum binding and was not due to a change in the dissociation constant for the ligand. The stimulation of adenylyl cyclase activity in the cell membrane by 1 μmol/l isoproterenol increased in lidocaine-treated cells. The increased number of receptors returned to the control level when the cells were cultured without lidocaine for a further 24 h. These results indicate that lidocaine up-regulates cardiac β-adrenoceptors at both clinical or toxic doses during the period of treatment. Other antiarrhythmic drugs such as disopyramide (Ia), mexiletine (lb) and flecainide (lc) also increased the number of β-receptors. It is suggested that when lidocaine or other class I antiarrhythmic drugs are used in cardiac disorders such as acute myocardial infarction and open-heart surgery, the responsiveness of the heart to catecholamines may be increased.