title: 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) (SSR149415), V(2) (SR121463) 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 (LF(BP) and LF/HF(HR)). 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 LF(BP) 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 BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) 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.
authors.affiliation: Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine University of Belgrade, P.O.Box 840, 11029 Belgrade, Republic of Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Stojicić
authors.forename: S
authors.initials: S
authors.lastname: Milutinović-Smiljanić
authors.forename: O
authors.initials: O
authors.lastname: Sarenac
authors.forename: S
authors.initials: S
authors.lastname: Milosavljević
authors.forename: J F R
authors.initials: JF
authors.lastname: Paton
authors.forename: D
authors.initials: D
authors.lastname: Murphy
authors.forename: N
authors.initials: N
authors.lastname: Japundzić-Zigon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005583:Fourier Analysis; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D017483:Receptors, Vasopressin / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D017483:Receptors, Vasopressin; D003345:Corticosterone