Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats

Abstract

To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V-1a (SR49059), V-1b (SSR 149415), V-2 (SR 121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LFBP and LF/HFHR). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LFBP oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V-1a, V-1b and V-2, receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V-1b and V-2 receptor antagonists reduced BPMAX whereas V-1a, V-1b antagonist and diazepam reduced HRMAX induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LFBP without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V-1b receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.