BETA-BLOCKERS AND THEIR ENANTIOMERS ANTAGONIZE THE ABERRANT SIGNAL TRANSDUCTION OF RAT MYOCARDIAL CELLS INDUCED BY TUMOR NECROSIS FACTOR-α

AIM: To investigate the effects of β-blockades and their enantiomers on the abnormal signal transduction of cultured myocardial cells of neonatal rats induced by tumor necrosis factor-α (TNFα). METHODS: The experiments were carried out in cultured myocardial cells from neonatal Wistar rats and were divided into 8 groups: (1) control; (2) given TNFα; (3) given TNFα plus S(-)-propranolol; (4) given TNFα plus R(+)-propranolol; (5) given TNFα plus S(-)-atenolol; (6) given TNFα plus R(+)-atenolol; (7) given TNFα plus carvedilol; (8) given TNFα plus SR59230A. RESULTS: The signal transduction of β-adrenergic receptors in rat myocardial cells was altered by TNFα: the densities of β-adrenergic receptors were downregulated (TNFα (0.95±0.31) pmol.mg^-1 (protein) vs control (2.08±0.07) pmol.mg^-1 (protein), P=0.004); Gs-protein was decreased and Gi-protein was increased, resulting in reduction of Gs/Gi ratios (TNFα 1.62±0.83 vs control 3.63±1.57, P<0.01); intracellular cAMP was raised (TNFα (7.88±0.58) pmol/106 cells vs control 4.0±0.34 pmol/106 cells, P<0.01); protein kinase-A (PKA) was activated (TNFα (2119±341) pmol.min^-1.mg^-1 (protein) vs control (1182±284) pmol.min^-1.mg^-1 (protein), P<0.01), and the levels of total PKA went up (TNFα(2449±390) pmol.min^-1.mg^-1 (protein) vs control (1836±311) pmol.min^-1.mg^-1 (protein), P<0.01). The effects of TNFα on G-proteins, cAMP and PKA can be weakened significantly by R(+)-propranolol, R(+)-atenolol and the third generation β-blockade carvedilol, but not weakened by S(-)-enantiomers of β-blockers. CONCLUSION: The R(+)-enantiomer of β-blockers was more effective to antagonize the aberrant effects of TNFα than S(-)-enantiomer. The R(+)-isomer may be a potential β-blocker to treat heart failure.