摘要
背景咪唑啉受体是重要的抗高血压药物作用位点,以往的研究认为胍丁胺是咪唑啉受体的内源性配体,但胍丁胺的中枢心血管效应及其机制研究不清楚。目的通过侧脑室注射的方法观察胍丁胺的中枢心血管效应及其机制,并探讨胍丁胺是否是咪唑啉受体的内源性配体。方法雄性SD大鼠70只,腹腔注射氨基甲酸乙酯1.0g/kg实施麻醉、气管插管、右侧股动、静脉插管,固定于立体定位仪。其中29只大鼠随机分为对照组、胍丁胺组(5、10、20μmol)和可乐定组(1.0μmol),以人工脑脊液为对照,给药后观察大鼠血压和心率变化。其余41只大鼠随机分为:①咪唑克生(咪唑啉受体阻断剂)+胍丁胺组;②MK-801[N-甲基-D-天门冬氨酸(NMDA)受体拮抗剂]+胍丁胺组;③可乐定+胍丁胺组;④人工脑脊液+胍丁胺组;⑤咪唑克生+可乐定组;⑥MK-801+可乐定组;⑦人工脑脊液+可乐定组。先分别侧脑室注射咪唑克生等阻断剂,10min后待血压平稳再分别侧脑室注射胍丁胺或可乐定,观察给药后大鼠的血压和心率变化。结果侧脑室注射胍丁胺5μmol[平均动脉压(MBP):给药前(113±5)比给药后(105±13)mmHg],10μmol[MBP:给药前(103±7)比给药后(72±9)mmHg](均P<0.05),胍丁胺均可显著降低麻醉大鼠血压,并减慢心率;侧脑室注射1.0μmol可乐定具有相似的心血管效应[MBP:给药前(92±8)比给药后(78±19)mmHg,P<0.05]。侧脑室注射等量人工脑脊液对麻醉大鼠的血压和心率不产生显著性作用。预先给予咪唑克生(1.0μmol)、NMDA受体拮抗剂MK-801(0.5μmol)或可乐定(1.0μmol)单独给药能显著减弱侧脑室注射胍丁胺的心血管效应;同时预先给予咪唑克生(1.0μmol)、NMDA受体拮抗剂MK-801(0.5μmol)也能有效减弱侧脑室注射可乐定产生的心血管效应。结论侧脑室注射胍丁胺产生的降低血压、减慢心率的作用可能是作用于咪唑啉受体产生,并且由NMDA受体介导的;可乐定能阻断胍丁胺的中枢心血管效应。
Background Irnidazoline receptors are important targets of anti-hypertension drug. Although previous studies indicated that agrnatine(Agm) is probable the endogenous ligand of imidazoline receptor, the cen- tral cardiovascular effects and mechanisms of the Agm were not clear. Objective To study the cardiovascular effects of Agm by injection of Agm into the lateral cerebral ventricle(ICV) in anesthetic rats and investigate its cardiovascular mechanisms by pre-application idazoxan, MK-801 or clonidine(Clo). Methods In seventy anes- thetized, spontaneously respired male SD rats, twenty-nine rats were randomized to receive following approaches: control, Agm 5, 10, 20 μmol and Clo 1.0 μmol injected into ICV to observe their central cardiovascular effects. Another forty one rats were pre-treated with idazoxan, MK-801, Clo, or aCSF and blood pressure(BP) and heart rate (HR) changes by 10μmol Agm or Clo were investigated. Results ICV of Agm 5 μmol [mean blood pres- sure(MBP) :(113±5) vs (105±13) mmHg] or 10μmol [(103±7) vs (72±9)mmHg](all P〈0.05) induced sig- nificantly decreased in BP and HR in anesthetized rats, analogue to the effect by ICV Clo [Clo 1.0 μmol, MBP: (92±8) vs (78± 19)rnmHg, P〈0.05]. The cardiovascular functions of ICV Agrn were significantly attenuated by pretreatment with central application of imidazoline receptor antagonistidazoxan, NMDA receptor antagonist MK-801 and were almost completely abolished by pretreatment with central application of Clo. Conclusion The bradycadia and hypotension of central Agm are the results of excitation of imidazoline receptors, which were mediated by NMDA receptors. Clo effectively abolish the central cardiovascular effect of Agm.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2009年第4期355-359,共5页
Chinese Journal of Hypertension
基金
国家自然科学基金资助项目(30700266)
陕西省卫生厅资助项目(06E05)
关键词
咪唑啉受体
胍丁胺
可乐定
侧脑室注射
心率
血压
Imidazoline receptors
Agmatine
Clonidine
Intracerebroventricular
Heart rate
Blood pressure