Cyclosporine impairs vasodilation without increased sympathetic activity in humans.
Cyclosporine impairs vasodilation without increased sympathetic activity in humans.
复制标题
环孢素会损害血管舒张，但不会增加人类的交感神经活动。
DOI：
10.1161/01.hyp.26.4.705
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Wood,AJ
中科院分区：
文献类型：
--
作者：
Stein,CM;He,H;Pincus,T;Wood,AJ
高血压和肾毒性经常使环孢素治疗复杂化；两种机制被认为是交感神经活性增加和血管反应性改变。在移植后接受环孢素治疗的患者中，由于伴随着主要的生理变化，很难评估这些机制。因此，我们对12名类风湿性关节炎患者进行了两次研究--服用环孢素和不服用环孢素。我们用线性变量差动变压器技术测量了手背静脉的血管反应。环孢素治疗显著减弱60 ng/min异丙肾上腺素(不加环孢素，19.8±3.5%比环孢素7.9±2.2%；P=0.02)和前列腺素E11000pg/分钟(不加环孢素，72.6±10.2%比环孢素45.6±9.0%)和2000pg/min(不加环孢素，100.8±14.7%比环孢素68.6±8.0%；F=5.47，P=0.047)引起的血管扩张。然而，环孢素不影响血管对苯肾上腺素或硝酸甘油的反应，也不影响用放射性同位素稀释法测量去甲肾上腺素溢出所评估的交感神经活性(无环孢素，516.1±47.9ngmin，环孢素476.6±51.8ngmin；P=.42)。环孢素可减弱两种激动剂的血管扩张作用，这两种激动剂通过腺苷环化酶起作用，但不改变α激动剂诱导的静脉收缩或交感神经活动。因此，人类长期服用环孢素后血管张力改变的一个重要机制可能是血管扩张受损，而不是交感神经激活或血管收缩增强。
Hypertension and nephrotoxicity frequently complicate treatment with cyclosporine; two suggested mechanisms are increased sympathetic activity and altered vascular reactivity. It is difficult to assess these mechanisms in patients receiving cyclosporine after transplantation because of the accompanying major physiological alterations. Therefore, we studied 12 patients with rheumatoid arthritis twice—while they were taking and not taking cyclosporine. We measured vascular response in the dorsal hand vein using the linear variable differential transformer technique. Cyclosporine treatment significantly attenuated vasodilation induced by 60 ng/min isoproterenol (no cyclosporine, 19.8±3.5% versus cyclosporine, 7.9±2.2%;P=.02) and prostaglandin E1at 1000 pg/min (no cyclosporine, 72.6±10.2% versus cyclosporine, 45.6±9.0%) and 2000 pg/min (no cyclosporine, 100.8±14.7% versus cyclosporine, 68.6±8.0%; F=5.47,P=.047). However, neither vascular response to phenylephrine or nitroglycerin nor sympathetic activity assessed by measurement of norepinephrine spillover with a radioisotope dilution technique was affected by cyclosporine (no cyclosporine, 516.1±47.9 ng/min versus cyclosporine, 476.6±51.8 ng/min;P=.42). Cyclosporine impaired venodilation in response to two agonists that act through adenylate cyclase without altering α-agonist–induced venoconstriction or sympathetic activity. Therefore, in humans impaired vasodilation rather than sympathetic activation or enhanced vasoconstriction may be an important mechanism for the alterations of vascular tone that occur after long-term cyclosporine administration.