Abstract 2371: L-Carnitine Prevents Alcohol-Induced Altered Cardiac TNF-α and Beta-Adrenergic Receptor (AR) Expression and Restores Normal Positive Inotropic Response to Beta-AR Stimulation after Short-Term Alcohol Consumption
Background. Chronic alcohol intake is associated with a diminished positive inotropic response to β-adrenergic receptor (AR) stimulation. Since recent studies reported improvement of β-adrenergic signal transduction by L-carnitine (LC) in the failing myocardium, we tested the hypothesis that LC may limit or prevent alcohol-induced adverse changes in cardiac TNF-α and β-AR expression and restore normal cardiac efficacy of β-AR stimulation after short-term alcohol consumption.
Methods. We compared left ventricular (LV) myocyte TNF-α and β1- and β3-AR expression and assessed LV and myocyte contractile response to isoproterenol (ISO) in 3 groups of adult rats over 8 –10 days: 13 received 20% alcohol (2 g/kg/day administered intragastrically); 12 received alcohol and LC (50 mg/kg i.p. daily, 60 min before ethanol); and 10 were controls.
Results. Compared with control myocytes, in alcoholic myocytes, TNF-α level (70%, 0.56 vs 0.33) was elevated. The level of β1-AR mRNA was decreased (33%, 0.62 vs 0.92), but β3-AR mRNA was increased (10%, 0.34 vs 0.31). These changes were associated with reduced LV and myocyte response to ISO (10-8 M). In controls, ISO increased LV contractility by 21% (MSW,109 vs 90 mmHg); in alcoholic rats, ISO increased MSW by 13% (65.0 vs 57.4 mmHg). Consistently, compared with control myocytes (C), in alcoholic myocytes (A), ISO caused a significantly less increase in dL/dtmax (A: 25%, 116 vs 93; C: 67%, 240 vs 143) and [Ca2+]iT (A: 16%, 0.21 vs 0.18; C: 32%, 0.33 vs 0.25). Compared with alcoholic myocytes, with concomitant LC, the alterations of cardiac levels of TNF-α (0.4), β1-AR (0.86), and β3-AR (0.32) were significantly decreased. Moreover, LV and myocyte contractile response to ISO were improved. In response to ISO stimulation, MSW (100.9 vs 84.8 mmHg ), dL/dtmax (225 vs 134 μm/s), and [Ca2+]iT (0.28 vs 0.23) increased about 19%, 57%, and 21%, respectively, which were similar to that achieved in the controls.
Conclusion. LC prevents alcohol-induced adverse changes in cardiac TNF-α and β1- and β3-AR expression and restores normal positive inotropic response to β-AR stimulation. Thus, LC may suggest a method to protect the β-adrenergic support for maintaining cardiac function in alcoholism.