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 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.
Teixeira de Castro
Renata Rodrigues
RR
Departament of Physiology and Pharmacology, Instituto Biomédico, Universidade Federal Fluminense, Rua Prof. Hernani Melo, 101 Niterói, RJ, Brazil CEP 24210-131.
Tibiriçá
Eduardo
E
de Oliveira
Marcos Aurélio Brazão
MA
Moreira
Paula Barbosa Baptista
PB
Catelli
Marcelo Flores
MF
Rocha
Nazareth Novaes
NN
Nóbrega
Antonio C L
AC
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010809:Physical Fitness / Q000502:physiology / Q000523:psychology; D000077769:Rilmenidine; D013315:Stress, Psychological / Q000503:physiopathology*
D000959:Antihypertensive Agents; D010080:Oxazoles; D000077769:Rilmenidine