The role of CRF1 receptors for sympathetic nervous response to laparotomy in anesthetized rats

Corticotropin-releasing factor (CRF) is released in response to various types of stressors and mediates endocrine, autonomic, immune, and behavioral responses to stress through interaction with CRF1 and CPT2 receptors. To investigate the role of CRF1 receptors in physiological responses to surgical stress, we analyzed the effects of two different non-peptide selective CRF1 receptor antagonists (JTC-017 and CP-154,526) and a peptide non-selective CRF receptor antagonist (astressin) on laparotomy-induced sympathetic nervous responses in isoflurane-anesthetized rats. JTC-017, CP-154,526, and astressin similarly suppressed plasma ACTH elevation induced by laparotomy. JTC-017 and CP-154,526 significantly augmented plasma noradrenaline and adrenaline responses to laparotomy, while astressin showed no effect on these responses. Laparotomy-induced maximum increases in mean blood pressure and heart rate were augmented by JTC-017, but were not affected by astressin. The results suggested for the first time that there was a pathway to attenuate sympathetic nervous response to surgical stress through CRF1 receptors in the central nervous system. (c) 2005 Elsevier B.V. All rights reserved.