Stojicić S, Milutinović-Smiljanić S, Sarenac O, Milosavljević S, Paton J F R, Murphy D, Japundzić-Zigon N
Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine University of Belgrade, P.O.Box 840, 11029 Belgrade, Republic of Serbia.
Neuropharmacology. 2008 Apr;54(5):824-36. doi: 10.1016/j.neuropharm.2007.12.013. Epub 2008 Jan 18.
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.
为研究中枢血管升压素受体对血压（BP）及心率（HR）对应激反应的作用，我们向自由活动的清醒大鼠侧脑室内注射非肽类选择性V(1a)（SR49059）、V(1b)（SSR149415）、V(2)（SR121463）受体拮抗剂、地西泮或赋形剂，通过向大鼠头部吹气2分钟使其应激。通过分析BP和HR的最大增加值（MAX）、最大反应潜伏期（LAT）、BP和HR曲线下的积分（integral）、恢复持续时间以及指示交感神经输出增加的BP和HR频谱参数（LF(BP)和LF/HF(HR)）来评估应激的心血管效应。此外，还测量了血清皮质酮的增加量。暴露于喷气应激会导致BP和HR同时升高，随后在恢复过程中逐渐下降，而LF(BP)振荡以及血清皮质酮水平仍保持升高。用血管升压素受体拮抗剂预处理的大鼠未出现镇静作用，而地西泮诱导的镇静作用在应激暴露期间持续存在。单独应用V(1a)、V(1b)和V(2)受体拮抗剂不会改变心血管参数的基础值，但可阻止积分(BP)的增加。此外，V(1b)和V(2)受体拮抗剂可降低BP(MAX)，而V(1a)、V(1b)拮抗剂和地西泮可降低喷气应激诱导的HR(MAX)。所有药物均缩短了恢复期，阻止了LF(BP)的增加，且不影响血清皮质酮水平的升高。结果表明，位于中枢神经系统内的血管升压素受体部分介导了对喷气应激的心血管反应，而不影响神经内分泌成分或诱导镇静作用。这些结果支持以下观点：V(1b)受体拮抗剂在降低应激相关疾病引起的动脉压方面可能具有潜在的治疗价值。
