Verwaerde P, Tran M A, Montastruc J L, Senard J M, Portolan G
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.
Fundam Clin Pharmacol. 1997;11(6):567-75. doi: 10.1111/j.1472-8206.1997.tb00862.x.
Yohimbine has been proposed for the treatment of neurogenic orthostatic hypotension; however, no controlled trial has been performed in experimental models of orthostatic hypotension or in patients with autonomic failure. The aim of the present study was to compare the effects of yohimbine (0.05 mg/kg, intravenously [i.v.]) and placebo (saline) in a new model of neurogenic orthostatic hypotension obtained by sinoaortic denervation (SAD) in chloralose-anaesthetized dogs. Blood pressure, heart rate, noradrenaline plasma levels and systolic blood pressure and heart rate short-term variabilities (calculated on low frequency [40-50 MHz] and high frequency [390-490 MHz] bands) were measured in supine position and after a 10 min 80 degrees head-up tilting. The drugs were administered in a double-blind cross-over randomized fashion. The head-up tilting performed in normal animals increased diastolic blood pressure (+12 +/- 4 mmHg), heart rate (+39 +/- 12 beats per minute [bpm]), the low frequency band of systolic blood pressure and noradrenaline plasma level, without changing systolic blood pressure or heart rate variability. In SAD dogs, a marked fall in systolic (-80 +/- 11 mmHg) and diastolic (-43 +/- 4 mmHg) blood pressures was observed within 1 min after placebo, without modification in heart rate, systolic blood pressure and heart rate short-term variabilities and noradrenaline plasma levels. In SAD dogs, yohimbine (0.05 mg/kg, i.v.) delayed the blood pressure fall elicited by head-up tilting, but failed to modify its magnitude. These results show that, in the model of orthostatic hypotension obtained by SAD, yohimbine, at an alpha 2-adrenoceptor selective dose (0.05 mg/kg), delays the fall in blood pressure elicited by head-up tilting. The effect of yohimbine can be explained by an increase in sympathetic tone.
育亨宾已被提议用于治疗神经源性直立性低血压；然而，尚未在直立性低血压的实验模型或自主神经功能衰竭患者中进行对照试验。本研究的目的是比较育亨宾（0.05 mg/kg，静脉注射[i.v.]）和安慰剂（生理盐水）在通过对水合氯醛麻醉的犬进行去窦弓神经支配（SAD）获得的神经源性直立性低血压新模型中的作用。在仰卧位以及10分钟80度头高位倾斜后，测量血压、心率、去甲肾上腺素血浆水平以及收缩压和心率的短期变异性（根据低频[40 - 50 MHz]和高频[390 - 490 MHz]频段计算）。药物以双盲交叉随机方式给药。正常动物进行头高位倾斜会使舒张压升高（+12±4 mmHg）、心率加快（+39±12次/分钟[bpm]）、收缩压的低频段以及去甲肾上腺素血浆水平升高，而收缩压或心率变异性不变。在SAD犬中，安慰剂给药后1分钟内观察到收缩压（-80±11 mmHg）和舒张压（-43±4 mmHg）显著下降，心率、收缩压和心率短期变异性以及去甲肾上腺素血浆水平无变化。在SAD犬中，育亨宾（0.05 mg/kg，静脉注射）延迟了头高位倾斜引起的血压下降，但未能改变其幅度。这些结果表明，在通过SAD获得的直立性低血压模型中，育亨宾在α2 - 肾上腺素能受体选择性剂量（0.05 mg/kg）下，延迟了头高位倾斜引起的血压下降。育亨宾的作用可以通过交感神经张力增加来解释。
