Teixeira de Castro Renata Rodrigues, Tibiriçá Eduardo, de Oliveira Marcos Aurélio Brazão, Moreira Paula Barbosa Baptista, Catelli Marcelo Flores, Rocha Nazareth Novaes, Nóbrega Antonio C L
Departament of Physiology and Pharmacology, Instituto Biomédico, Universidade Federal Fluminense, Rua Prof. Hernani Melo, 101 Niterói, RJ, Brazil CEP 24210-131.
Cardiovasc Drugs Ther. 2006 Apr;20(2):129-34. doi: 10.1007/s10557-006-7653-8.
Activation of the sympathetic nervous system plays a major role in the pathogenesis and prognosis of cardiovascular diseases. Rilmenidine is an I(1)-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 (VO(2max) - 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.
交感神经系统的激活在心血管疾病的发病机制和预后中起主要作用。利美尼定是一种I(1)-咪唑啉受体激动剂，可通过调节中枢交感神经活动来降低血压，但低剂量利美尼定对增加肾上腺素能驱动的生理操作所引起的血流动力学反应的影响尚不清楚。为了评估低剂量利美尼定对应激血流动力学反应的影响，32名健康受试者（20 - 56岁）在随机、双盲、安慰剂对照的交叉研究中，口服0.5毫克利美尼定（RIL）或安慰剂（PLA）两小时后，进行了急性体育锻炼（n = 15，跑步机上的个体化斜坡方案）和精神应激（n = 17，文字颜色Stroop测试和心算测试）。没有受试者抱怨任何副作用。利美尼定降低了运动峰值心率（PLA：187±7；RIL：181±9次/分钟；P = 0.003），但未改变峰值有氧功率（VO(2max) - PLA：41.7±6.2；RIL：42.3±6.7毫升/千克/分钟；P = 0.26）。在精神应激期间，利美尼定抑制了收缩压峰值（PLA：123±10；RIL：114±8毫米汞柱；P = 0.02）和舒张压峰值（PLA：86±7；RIL：81±7毫米汞柱；P <0.05）的血压反应。总之，利美尼定降低了对身体和精神应激刺激的血流动力学反应，而不限制运动能力。这些结果支持了这样一种观点，即低于治疗高血压推荐剂量的利美尼定降低了应激时的心肌需氧量，可能具有潜在的临床意义。
