Reduced Hemodynamic Responses to Physical and Mental Stress Under Low-Dose Rilmenidine in Healthy Subjects

Activation of the sympathetic nervous system plays a major role in the pathogenesis and prognosis of cardiovascular diseases. Rilmenidine is an I1-imidazoline receptor agonist that reduces blood pressure by modulation of central sympathetic activity, but the effects of low-dose rilmenidine on the hemodynamic responses to physiological maneuvers that increase adrenergic drive is not known. To assess the effects of low-dose rilmenidine on the hemodynamic responses to stress, 32 healthy subjects (20–56 years old) underwent acute physical exercise (n = 15, individualized ramp protocol on treadmill) and mental stress (n = 17, word color Stroop and mental arithmetics tests) two hours after the oral administration of 0.5 mg of rilmenidine (RIL) or placebo (PLA) following a randomized, double-blind, placebo controlled crossover study. No subject complained of any side effect. Rilmenidine reduced peak exercise heart rate (PLA: 187 ± 7; RIL: 181 ± 9 bpm; P = 0.003), but did not modify peak aerobic power (VO2max — PLA: 41.7 ± 6.2; RIL: 42.3 ± 6.7 ml/kg/min; P = 0.26). During mental stress, rilmenidine inhibited the peak systolic (PLA: 123 ± 10; RIL: 114 ± 8 mmHg; P = 0.02) and diastolic (PLA: 86 ± 7; RIL: 81 ± 7 mmHg; P <0.05) blood pressure responses. In conclusion, rilmenidine reduced the hemodynamic response to physical and mental stress stimuli without limiting exercise capacity. These results support the concept that rilmenidine, at a dose lower than the ones recommended to treat hypertension, reduced the myocardial oxygen demand to stress and may carry potential clinical impact.