Floras J S, Aylward P E, Victor R G, Mark A L, Abboud F M
Department of Internal Medicine, University of Iowa College of Medicine, University of Iowa Hospitals and Clinics, Iowa City 52242.
J Clin Invest. 1988 Apr;81(4):1265-74. doi: 10.1172/JCI113444.
Numerous studies have suggested that epinephrine may facilitate neural release of NE. There have been no studies in humans that demonstrate the functional significance of this action. To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure [LBNP]) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery. These doses had no systemic effects. We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism). Studies were done on 23 normal male volunteers. Forearm blood flow was measured with a strain gauge plethysmograph and intraarterial pressure was recorded. The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE. This ratio increased during infusions of both epinephrine and isoproterenol. 30 min after epinephrine the vasoconstrictor response to LBNP (n = 15) was augmented from +9.9 +/- 2.2 (SE) resistance units (RU) before epinephrine to +16.4 +/- 3.2 RU (P less than 0.05); whereas the response to NE (n = 8) tended to decrease from +8.8 +/- 3.1 RU before to +4.2 +/- 1.2 RU after epinephrine (P greater than 0.05). In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol. The augmented ratio of responses to LBNP/NE after epinephrine and not after isoproterenol supports the concept that epinephrine, but not isoproterenol, is taken up by the adrenergic terminal, is released subsequently during reflex stimulation, and augments the release of the neurotransmitter NE. These experiments provide the first hemodynamic evidence in humans that epinephrine and isoproterenol facilitate neurogenic vasoconstriction. The sustained effect of epinephrine in contrast to isoproterenol suggests that the late facilitation by epinephrine is related to its neural uptake and subsequent release.
大量研究表明，肾上腺素可能促进去甲肾上腺素的神经释放。目前尚无人体研究证明这一作用的功能意义。为了确定肾上腺素是否能促进人体神经源性血管收缩，我们对比了在向肱动脉输注肾上腺素（50纳克/分钟）或异丙肾上腺素（10或25纳克/分钟）之前、期间及之后30分钟，前臂血管收缩剂对反射刺激（下体负压[LBNP]）和动脉内去甲肾上腺素的反应。这些剂量无全身效应。我们推断，如果肾上腺素和异丙肾上腺素对β受体的节前刺激具有功能意义，那么与对去甲肾上腺素的反应（节后机制）相比，对LBNP的血管收缩反应将会增强。研究在23名正常男性志愿者身上进行。用应变片体积描记器测量前臂血流量，并记录动脉内压力。血管收缩剂对LBNP/去甲肾上腺素的反应比值用作神经递质去甲肾上腺素神经释放的指标。在输注肾上腺素和异丙肾上腺素期间，该比值均升高。肾上腺素输注30分钟后，对LBNP的血管收缩反应（n = 15）从肾上腺素输注前的+9.9±2.2（标准误）阻力单位（RU）增至+16.4±3.2 RU（P<0.05）；而对去甲肾上腺素的反应（n = 8）则倾向于从输注前的+8.8±3.1 RU降至肾上腺素输注后的+4.2±1.2 RU（P>0.05）。相比之下，异丙肾上腺素输注30分钟后，对LBNP和去甲肾上腺素的血管收缩反应与输注前相同。肾上腺素输注后而非异丙肾上腺素输注后LBNP/去甲肾上腺素反应比值增加，支持了这样一种观点，即肾上腺素而非异丙肾上腺素被肾上腺素能末梢摄取，随后在反射刺激期间释放，并增强神经递质去甲肾上腺素的释放。这些实验为人体提供了首个血流动力学证据，证明肾上腺素和异丙肾上腺素能促进神经源性血管收缩。与异丙肾上腺素相比，肾上腺素的持续效应表明，肾上腺素的后期促进作用与其神经摄取及随后的释放有关。
