Stress-triggered changes in peripheral catecholaminergic systems.
- Author(s): Kvetnansky, Richard
- Lu, Xiaojiong
- Ziegler, Michael G
- et al.
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.