Corticotropin-releasing factor receptor-1: a therapeutic target for cardiac autonomic disturbances.
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 (CRF(1)) antagonists increase cardiac vagal and decrease sympathetic activity, thereby also implicating CRF(1) as a therapeutic target for autonomic disturbances resulting in elevated sympathetic activity, such as hypertension and coronary heart disease. The central distribution of CRF(1) and the cardiovascular effects of CRF(1) agonists and antagonists, suggest it mediates CRF-induced autonomic changes. However, there is insufficient information regarding the autonomic effects of CRF(2)-selective compounds to rule out CRF(2) contribution. This review provides an update on the autonomic effects of CRF and the neuronal projections thought to mediate these cardiovascular responses.
Wood
Susan K
SK
Children's Hospital of Philadelphia, Division of Stress Neurobiology, 3615 Civic Ctr Blvd, ARC Rm. 409G, Philadelphia, PA 19104, USA. susankwood2@gmail.com
Woods
James H
JH
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology*; D002320:Cardiovascular Physiological Phenomena; D002490:Central Nervous System / Q000502:physiology / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone