EFFECT OF CALCIUM-CHANNEL ANTAGONISTS ON THE CARDIAC VAGAL TONE RESPONSE TO SUBMAXIMAL EXERCISE

Reductions in cardiac vagal tone have been shown to correlate with a greater susceptibility to ventricular fibrillation. Calcium antagonists have been shown to protect against malignant arrhythmias probably as the result of direct actions on cardiac muscle. However, these drugs could also reflexively alter cardiac vagal tone as a consequence of reductions in arterial pressure. Therefore, the effects of various calcium channel antagonists on cardiac vagal tone, both at rest and during exercise, were investigated. The R-R interval was recorded in chronically instrumented mongrel dogs (n = 39) and the amplitude of the respiratory sinus arrhythmia (0.24-1.04 Hz) was calculated using time-series analysis techniques. Before exercise, verapamil (n = 17, 250 mug/kg), nifedipine (n = 5, 10 mug/kg; n9, 1 00 mug/kg), diltiazem (n = 1 0, 1,000 mug/kg), Ro 40-5967 (n = 14, 1,000 mug/kg), and magnesium sulfate (n = 10,100 mg/kg) significantly increased heart rate, while flunarizine (n = 11, 2.5 mg/kg) and a lower dose of Ro 40-5967 (n = 5, 250 mug/kg) did not affect heart rate. During exercise, nifedipine (high dose) increased heart rate, while Ro 40-5967 (high dose) decreased heart rate. All six drugs reduced vagal tone before exercise; magnesium and nifedipine (high dose) elicited the greatest reduction, while flunarizine produced the smallest decrease. The vagal tone response to exercise was not affected by flunarizine and Ro 40-5967 (low dose), but it was accentuated by magnesium, nifedipine, and verapamil. Intermediate responses were noted for Ro-40-5967 (high dose) and diltiazem. Pronounced hemodynamic effects were noted for flunarizine, magnesium, nifedipine, and verapamil, but not for Ro 40-5967. Thus, calcium antagonists have variable hemodynamic profiles and can elicit pronounced reductions in cardiac vagal tone, presumably due to activation of the baroreceptor reflex.