Rubin P C, Blaschke T F
Br J Clin Pharmacol. 1980 Jul;10(1):23-32. doi: 10.1111/j.1365-2125.1980.tb00498.x.
Cardiovascular, catecholamine and neuroendocrine changes were studied following administration of prazosin to ten normal subjects. In response to a fall in standing blood pressure from 87±5 (s.d.) mmHg to 49±20 ( < 0.01) heart rate (measured by continuous ECG monitoring) rose from 81±11 to 118±20 ( < 0.01). Five of the ten subjects sustained their tachycardia on standing and developed at most mild symptoms. In the other five, tachycardia suddenly gave way to bradycardia and they became syncopal. In the supine position, when blood pressure was not significantly different from control, plasma noradrenaline concentration (nmol/l) was 2±0.5 compared with a control value of 1.2±0.3 ( < 0.01). In response to standing hypotension plasma noradrenaline was 4.2±2.7 compared with a standing control value of 1.9±0.4 ( < 0.02). Four hours after taking prazosin five of the subjects stood for 30 min and blood was drawn for plasma renin activity (PRA). Blood pressure at this time was 15 mmHg below control ( < 0.02). PRA (ng ml h) was 6.4±2.3 compared with time matched placebo control of 1.4±0.8 ( < 0.01). At the same time as the PRA sampling, plasma cortisol was 15.6±2.6 μg/100 ml during hypotension and 8.2±3.9 following placebo ( < 0.01). Growth hormone was 1.4±0.3 ng/ml during hypotension and 1.0±0.2 following placebo ( < 0.01). Prolactin did not rise significantly during hypotension induced by prazosin. Isoprenaline infusion produced the same change in heart rate during the time of maximum prazosin action as when given alone. It is concluded that these observations are not in keeping with earlier reports that prazosin lowers blood pressure without producing a reflex increase in heart rate or renin release. Nor are these findings in keeping with current theories of the mechanism of action of prazosin which variously suggest that noradrenaline concentration should not increase, or that the heart is incapable of responding to an adrenergic stimulus in the presence of prazosin.
对10名正常受试者服用哌唑嗪后的心血管、儿茶酚胺和神经内分泌变化进行了研究。站立时血压从87±5（标准差）mmHg降至49±20（<0.01），心率（通过连续心电图监测测量）从81±11升至118±20（<0.01）。10名受试者中有5名站立时维持心动过速，至多出现轻微症状。另外5名受试者心动过速突然转为心动过缓，并出现晕厥。仰卧位时，血压与对照组无显著差异，血浆去甲肾上腺素浓度（nmol/l）为2±0.5，而对照值为1.2±0.3（<0.01）。对站立性低血压的反应中，血浆去甲肾上腺素为4.2±2.7，而站立对照值为1.9±0.4（<0.02）。服用哌唑嗪4小时后，5名受试者站立30分钟，抽取血液检测血浆肾素活性（PRA）。此时血压比对照低15 mmHg（<0.02）。PRA（ng ml/h）为6.4±2.3，而时间匹配的安慰剂对照为1.4±0.8（<0.01）。在采集PRA样本的同时，低血压时血浆皮质醇为15.6±2.6μg/100 ml，服用安慰剂后为8.2±3.9（<0.01）。低血压时生长激素为1.4±0.3 ng/ml，服用安慰剂后为1.0±0.2（<0.01）。哌唑嗪诱导的低血压期间催乳素未显著升高。在哌唑嗪作用最强时，静脉输注异丙肾上腺素引起的心率变化与单独给药时相同。结论是，这些观察结果与早期报道不符，早期报道称哌唑嗪降低血压但不会引起心率反射性增加或肾素释放。这些发现也与目前关于哌唑嗪作用机制的理论不符，这些理论分别表明去甲肾上腺素浓度不应增加，或者在哌唑嗪存在的情况下心脏无法对肾上腺素能刺激作出反应。
