Lenders J W, Golczynska A, Goldstein D S
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Endocrinol Metab. 1995 Jun;80(6):1804-8. doi: 10.1210/jcem.80.6.7775627.
The sympathetic nervous system and the pituitary-adrenocortical system are two of the body's main stress effector systems. Animal studies have indicated that exogenously administered glucocorticoids inhibit sympathetic outflows and interfere with the function of presynaptic alpha 2-adrenoceptors modulating neuronal norepinephrine (NE) release. The present study tested whether glucocorticoids produce similar effects in humans. In a randomized, double-blind, placebo-controlled cross-over experiment, 15 healthy subjects took 20 mg prednisone or placebo orally daily each morning for 1 week, followed by the other drug after a 1-week washout. On the last day of each treatment week, blood samples were drawn for assays of plasma levels of catechols and ACTH before and after iv infusion of the alpha 2-adrenoceptor antagonist yohimbine (YOH) (0.125 mg/kg bolus, 0.001 mg.kg-1.min-1 infusion). In 7 subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity (MSNA) was also measured at baseline and after YOH infusion at the end of both treatment weeks. Prednisone decreased plasma NE levels and MSNA compared with levels after placebo (1.09 +/- 0.11 nmol/L vs. 1.40 +/- 0.13 nmol/L, P < 0.01; 30 +/- 4 bursts/min vs. 36 +/- 3 bursts/min, P < 0.05) without affecting blood pressure or pulse rate. YOH increased mean arterial blood pressure by 12% (P < 0.001) and heart rate by 7% (P < 0.05); prednisone did not alter these effects of YOH. YOH-induced proportionate increments in plasma NE levels averaged about 10 times those in MSNA. Prednisone did not affect the YOH-induced proportionate increments in plasma NE levels (placebo, 243%; prednisone, 237%) or MSNA (placebo, 22%; prednisone, 23%). The decrements in MSNA and plasma NE levels after prednisone treatment indicate that glucocorticoids inhibit sympathoneural outflows in humans. The 10-fold larger NE than MSNA response to YOH confirms substantial inhibitory modulation of NE release by alpha 2-adrenoceptors on noradrenergic terminals, and the similarity of responses to YOH after prednisone or placebo suggests that glucocorticoid-induced sympathoinhibition occurs independently of altered modulatory function of alpha 2-adrenoceptors on noradrenergic terminals.
交感神经系统和垂体 - 肾上腺皮质系统是人体主要的应激效应系统中的两个。动物研究表明，外源性给予糖皮质激素会抑制交感神经输出，并干扰调节神经元去甲肾上腺素（NE）释放的突触前α2 - 肾上腺素能受体的功能。本研究测试了糖皮质激素在人类中是否产生类似的效应。在一项随机、双盲、安慰剂对照的交叉实验中，15名健康受试者每天早晨口服20毫克泼尼松或安慰剂，持续1周，在1周的洗脱期后服用另一种药物。在每个治疗周的最后一天，静脉注射α2 - 肾上腺素能受体拮抗剂育亨宾（YOH）（0.125毫克/千克推注，0.001毫克·千克-1·分钟-1输注）前后采集血样，测定血浆儿茶酚胺和促肾上腺皮质激素（ACTH）水平。在7名受试者中，还在两个治疗周结束时的基线和YOH输注后直接记录腓骨骨骼肌交感神经活动（MSNA）。与安慰剂后的水平相比，泼尼松降低了血浆NE水平和MSNA（1.09±0.11纳摩尔/升对1.40±0.13纳摩尔/升，P<0.01；30±4次爆发/分钟对36±3次爆发/分钟，P<0.05），而不影响血压或脉搏率。YOH使平均动脉血压升高12%（P<0.001），心率升高7%（P<0.05）；泼尼松未改变YOH的这些效应。YOH诱导的血浆NE水平的成比例增加平均约为MSNA增加的10倍。泼尼松不影响YOH诱导的血浆NE水平（安慰剂，243%；泼尼松，237%）或MSNA（安慰剂，22%；泼尼松，23%）的成比例增加。泼尼松治疗后MSNA和血浆NE水平的降低表明糖皮质激素抑制人类的交感神经流出。对YOH的NE反应比对MSNA反应大10倍，证实了α2 - 肾上腺素能受体对去甲肾上腺素能终末NE释放的显著抑制调节作用，并且泼尼松或安慰剂后对YOH的反应相似，表明糖皮质激素诱导的交感神经抑制独立于α2 - 肾上腺素能受体对去甲肾上腺素能终末调节功能的改变而发生。
