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

Abstract 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 CRF 1 and CRF 2 receptors. To investigate the role of CRF 1 receptors in physiological responses to surgical stress, we analyzed the effects of two different non-peptide selective CRF 1 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 CRF 1 receptors in the central nervous system.