Jacobs M C, Lenders J W, Willemsen J J, Thien T
Department of Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
J Hypertens. 1995 Dec;13(12 Pt 2):1837-41.
Doxazosin, a selective alpha1-adrenoceptor antagonist, lowers blood pressure by reducing peripheral vascular resistance without causing reflex tachycardia. To discover whether antihypertensive treatment with an alpha1-adrenoceptor blocker is accompanied by an increase in sympathoadrenomedullary activity, we studied plasma catecholamine kinetics before and during treatment with doxazosin.
Eleven patients with essential hypertension were studied before and after 3 months' treatment with doxazosin (4-8 mg a day). 3H-noradrenaline and 3H-adrenaline were infused simultaneously and blood samples were collected to calculate plasma catecholamine kinetics before and during sympatho-adrenomedullary stimulation (lower-body negative pressure).
Doxazosin decreased systolic and diastolic blood pressure and forearm vascular resistance, whereas the heart rate did not change significantly. During doxazosin, baseline arterial plasma noradrenaline increased from 0.97 +/- 0.07 to 1.21 +/- 0.07 nmol/l, and this appeared to be due to an increase in total body noradrenaline spillover from 1.54 +/- 0.15 to 1.84 +/- 0.16 nmol/min; noradrenaline clearance did not change significantly. Forearm noradrenaline spillover also increased, from 0.89 +/- 0.18 to 1.48 +/- 0.23 pmol/100 ml per min. In contrast, arterial plasma adrenaline, total body adrenaline spillover and adrenaline clearance were not significantly affected by doxazosin treatment. The response of plasma noradrenaline and total body and forearm spillover of noradrenaline to lower-body negative pressure (-40 mmHg) was significantly increased during doxazosin administration, whereas the response of the adrenaline kinetic parameters were not altered.
The blood pressure reduction induced by a chronic administration of the alpha1-adrenoceptor blocker doxazosin elicits a baroreceptor-mediated reflexive increase in sympathoneural but not in adrenomedullary activity. The latter finding might partly explain why the heart rate is not increased during chronic treatment with this alpha1-adrenoceptor blocking drug.
多沙唑嗪是一种选择性α1肾上腺素能受体拮抗剂，通过降低外周血管阻力来降低血压，且不会引起反射性心动过速。为了探究使用α1肾上腺素能受体阻滞剂进行降压治疗是否会伴随交感肾上腺髓质活动增加，我们研究了多沙唑嗪治疗前及治疗期间的血浆儿茶酚胺动力学。
对11例原发性高血压患者在接受多沙唑嗪（每日4 - 8毫克）治疗3个月前后进行了研究。同时输注3H - 去甲肾上腺素和3H - 肾上腺素，并采集血样以计算在交感肾上腺髓质刺激（下体负压）前及期间的血浆儿茶酚胺动力学。
多沙唑嗪降低了收缩压和舒张压以及前臂血管阻力，而心率无显著变化。在使用多沙唑嗪期间，动脉血浆去甲肾上腺素基线值从0.97±0.07纳摩尔/升增至1.21±0.07纳摩尔/升，这似乎是由于全身去甲肾上腺素溢出量从1.54±0.15纳摩尔/分钟增至1.84±0.16纳摩尔/分钟；去甲肾上腺素清除率无显著变化。前臂去甲肾上腺素溢出量也增加，从0.89±0.18皮摩尔/100毫升每分钟增至1.48±0.23皮摩尔/100毫升每分钟。相比之下，动脉血浆肾上腺素、全身肾上腺素溢出量和肾上腺素清除率未受到多沙唑嗪治疗的显著影响。在使用多沙唑嗪期间，血浆去甲肾上腺素以及全身和前臂去甲肾上腺素溢出量对下体负压（-40毫米汞柱）的反应显著增强，而肾上腺素动力学参数的反应未改变。
长期使用α1肾上腺素能受体阻滞剂多沙唑嗪引起的血压降低引发了压力感受器介导的交感神经活动反射性增加，但肾上腺髓质活动未增加。后一发现可能部分解释了为何使用这种α1肾上腺素能受体阻断药物进行长期治疗期间心率未增加。
