Taddei S, Salvetti A, Pedrinelli R
Hypertension Unit, I Clinica Medica, University of Pisa, Italy.
Circulation. 1989 Sep;80(3):485-90. doi: 10.1161/01.cir.80.3.485.
Sympathetic vasoconstriction not mediated by alpha-adrenoceptors has been identified in vitro and in animals but not in humans. We evaluated the effect of alpha-adrenoceptor blockade on either endogenous vascular sympathetic activation (obtained through the application of a nonhypotensive lower-body negative pressure, -10 mm Hg for 5 minutes) or selective postsynaptic alpha-adrenoceptor stimulation by exogenous norepinephrine (0.005 micrograms/100 ml forearm tissue/min for 3 minutes) in the presence of beta-blockade by propranolol (10 micrograms/100 ml forearm tissue/min for 15 minutes). Drugs were infused into the brachial artery at systemically ineffective rates while continuously monitoring forearm blood flow (by venous plethysmography), intra-arterial mean arterial pressure, and heart rate in patients with essential hypertension. The irreversible antagonist phenoxybenzamine was used at a rate of 20 micrograms/100 ml forearm tissue/min for 1 hour, which antagonized the local responses to norepinephrine in a range of 0.005-0.05 micrograms/100 ml forearm tissue/min. During saline administration, either lower-body negative pressure or exogenous norepinephrine decreased forearm blood flow comparably. However, after phenoxybenzamine administration, forearm vasoconstriction to norepinephrine was abolished while a residual response to lower-body negative pressure remained in each patient. To exclude insufficient alpha-adrenoceptor blockade, the same experimental protocol was repeated by doubling phenoxybenzamine concentrations. No difference from the data obtained with the lower level of antagonist was found. Further studies were performed to confirm the sympathetic origin of the residual vasoconstriction. Bretylium tosylate, a neurotransmitter blocker, infused into the brachial artery (50 micrograms/100 ml forearm tissue/min for 90 minutes) abolished the effect of endogenous sympathetic activation but did not alter the effect of exogenous norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
在体外和动物实验中已证实存在不由α-肾上腺素能受体介导的交感神经血管收缩，但在人体中尚未发现。我们评估了α-肾上腺素能受体阻滞剂对内源性血管交感神经激活（通过施加非降压性的下体负压，-10 mmHg持续5分钟获得）或在外源性去甲肾上腺素（0.005微克/100毫升前臂组织/分钟，持续3分钟）选择性刺激突触后α-肾上腺素能受体的影响，同时使用普萘洛尔进行β受体阻滞（10微克/100毫升前臂组织/分钟，持续15分钟）。以全身无效的速率将药物注入肱动脉，同时持续监测原发性高血压患者的前臂血流量（通过静脉体积描记法）、动脉内平均动脉压和心率。使用不可逆拮抗剂酚苄明，速率为20微克/100毫升前臂组织/分钟，持续1小时，可拮抗0.005 - 0.05微克/100毫升前臂组织/分钟范围内对去甲肾上腺素的局部反应。在给予生理盐水期间，下体负压或外源性去甲肾上腺素对前臂血流量的降低作用相当。然而，在给予酚苄明后，对去甲肾上腺素的前臂血管收缩作用被消除，而每个患者对下体负压仍有残余反应。为排除α-肾上腺素能受体阻滞不足，将酚苄明浓度加倍重复相同实验方案。未发现与较低拮抗剂水平获得的数据有差异。进行了进一步研究以证实残余血管收缩的交感神经起源。将神经递质阻滞剂溴苄铵注入肱动脉（50微克/100毫升前臂组织/分钟，持续90分钟）可消除内源性交感神经激活的作用，但不改变外源性去甲肾上腺素的作用。（摘要截短于250字）
