Corticotropin-releasing factor receptor-1: a therapeutic target for cardiac automatic disturbances

被引:41
作者
Wood, Susan K.
Woods, James H.
机构
[1] Childrens Hosp Philadelphia, Stress Neurobiol Div, Philadelphia, PA 19104 USA
[2] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA
关键词
cardiac vagal activity; corticotropin-releasing factor; heart rate variability; sympathetic nervous system; DORSAL MOTOR NUCLEUS; MIDBRAIN PERIAQUEDUCTAL GRAY; VAGAL PREGANGLIONIC NEURONS; SYMPATHETIC-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; ANXIETY-LIKE BEHAVIOR; HEART-RATE; IN-VITRO; NORADRENERGIC SYSTEM; TRACTUS-SOLITARIUS;
D O I
10.1517/14728222.11.11.1401
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Corticotropin-releasing factor (CRF), a neuropeptide involved in triggering a myriad of responses to fear and stress, is favourably positioned in the CNS to modulate the sympathetic and parasympathetic branches of the cardiac autonomic nervous system. In vivo studies suggest that central CRF inhibits vagal output and stimulates sympathetic activity. Therefore, CRF may function to inhibit exaggerated vagal activation that results in severe bradycardia or even vasovagal syncope. On the other hand, CRF receptor-1 (CRF1) antagonists increase cardiac vagal and decrease sympathetic activity, thereby also implicating CRF, as a therapeutic target for autonomic disturbances resulting in elevated sympathetic activity, such as hypertension and coronary heart disease. The central distribution of CRF, and the cardiovascular effects of CRF, agonists and antagonists, suggest it mediates CRF-induced autonomic changes. However, there is insufficient information regarding the autonomic effects of CRF2-selective compounds to rule out CRF2 contribution. This review provides an update on the autonomic effects of CRF and the neuronal projections thought to mediate these cardiovascular responses.
引用
收藏
页码:1401 / 1413
页数:13
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