Kvetnansky Richard, Lu Xiaojiong, Ziegler Michael G
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Adv Pharmacol. 2013;68:359-97. doi: 10.1016/B978-0-12-411512-5.00017-8.
The sympathetic nervous system not only regulates cardiovascular and metabolic responses to stress but also is altered by stress. The sympathoneural and sympathoadrenomedullary systems are modified by different metabolic pathways and have different responses to short- and to long-term stressors. Stress also induces nonneuronal catecholamine enzymes, primarily through corticosteroids. Catecholamine synthetic enzymes are induced by different pathways in response to short- and long-term acting stressors, like cold exposure or immobilization, and differently in the sympathetic ganglia and the adrenal medulla. However, a long-term exposure to one stressor can increase the response to a second, different stressor. Tyrosine hydroxylase gene transcription increases after only 5min of immobilization through phosphorylation of CREB, but this response is short lived. However, repeated stress gives a longer-lived response utilizing transcription factors such as Egr-1 and Fra-2. Glucocorticoids and ACTH also induce sympathoneural enzymes leading to distinct patterns of short-term and long-lived activation of the sympathetic nervous system. Nonneuronal phenylethanolamine N-methyltransferase (PNMT) develops early in the heart and then diminishes. However, intrinsic cardiac adrenergic cells remain and nonneuronal PNMT is present in many cells of the adult organism and increases in response to glucocorticoids. Both stress-induced and administered glucocorticoids induce fetal PNMT and hypertension. Human stressors such as caring for an ill spouse or sleep apnea cause a persistent increase in blood norepinephrine, increased blood pressure, and downregulated catecholamine receptors. Hypertension is associated with a loss of slow-wave sleep, when sympathetic nerve activity is lowest. These findings indicate that stress-induced alteration of the sympathetic nervous system occurs in man as in experimental animals.
交感神经系统不仅调节对压力的心血管和代谢反应，而且也会因压力而发生改变。交感神经和交感肾上腺髓质系统通过不同的代谢途径进行调节，对短期和长期应激源有不同的反应。压力还主要通过皮质类固醇诱导非神经元儿茶酚胺酶。儿茶酚胺合成酶通过不同途径被短期和长期作用的应激源诱导，如冷暴露或制动，在交感神经节和肾上腺髓质中的诱导方式不同。然而，长期暴露于一种应激源会增加对第二种不同应激源的反应。酪氨酸羟化酶基因转录在制动仅5分钟后通过CREB磷酸化而增加，但这种反应是短暂的。然而，反复应激利用Egr-1和Fra-2等转录因子产生更持久的反应。糖皮质激素和促肾上腺皮质激素也诱导交感神经酶，导致交感神经系统短期和长期激活的不同模式。非神经元苯乙醇胺N-甲基转移酶（PNMT）在心脏中早期发育，然后减少。然而，心脏内在的肾上腺素能细胞仍然存在，非神经元PNMT存在于成年生物体的许多细胞中，并对糖皮质激素产生反应而增加。应激诱导和给予的糖皮质激素都会诱导胎儿PNMT和高血压。诸如照顾生病配偶或睡眠呼吸暂停等人类应激源会导致血液去甲肾上腺素持续增加、血压升高和儿茶酚胺受体下调。高血压与慢波睡眠丧失有关，此时交感神经活动最低。这些发现表明，应激诱导的交感神经系统改变在人类中与实验动物中一样会发生。
