Differential effects of metoprolol and atenolol to neuropeptide Y blockade in coronary artery disease

OBJECTIVE: To explore possible differential effects between metoprolol and atenolol in patients with coronary artery disease. DESIGN: The study was randomized, double blind, two-way crossover with the Y1 antagonist AR-H040922 given as IV infusion for 2 h or placebo. Most patients were treated with metoprolol or atenolol. In a post hoc analysis we compared the hemodynamic response to exercise of the Y1 antagonist in patients on metoprolol (n = 16) and atenolol (n = 5), and assessed respiratory sinus arrhythmia (RSA), an indirect measurement of cardiac vagal activation, in the placebo phase in patients on metoprolol (n = 26) and on atenolol (n = 24). RESULTS: 1) The Y1 antagonist reduced the systolic blood pressure rise during and after exercise during atenolol, but not during metoprolol, while heart rate and maximal load were similar with the two beta-blockers and not affected by the Y1 antagonist. 2) At equal heart- and respiration-rate 7-8 min after exercise the RSA was significantly lower in atenolol than in metoprolol patients, while no difference was seen at rest before exercise. CONCLUSION: These findings from this hypothesis generating study indicate that peripheral effects of NPY contribute less to cardiovascular stress reactions in patients on metoprolol than in those on atenolol.