中枢γ-氨基丁酸对清醒活动高血压大鼠血压的影响

Effect of central gamma-aminobutyric acid on the regulation of blood pressure in conscious,unrestrained spontaneously hypertensive rats

目的研究中枢γ-氨基丁酸对清醒活动自发性高血压大鼠(SHR)血压及动脉压力感受性反射功能(BRS)的影响。方法应用监测清醒活动大鼠血流动力学变化的手段,以W istar-Kyoto大鼠(WKY)为对照组,SHR为实验组,两组动物侧脑室注射γ-氨基丁酸10μmol、蝇蕈醇30 nmol、荷包牡丹碱3 nmol,观察清醒实验动物腹主动脉平均动脉压的变化;应用改良的Smyth方法,观察动脉压力感受性反射敏感性的改变。结果与侧脑室注射人工脑脊液相比,侧脑室注射γ-氨基丁酸和蝇蕈醇,可使SHR血压明显下降、BRS明显上升,且使SHR血压下降幅度及BRS增加幅度比WKY大鼠更为显著;侧脑室注射荷包牡丹碱可使SHR血压明显上升,上升幅度比WKY明显,并能使SHR BRS明显下降。结论中枢GABA能够降低血压,改善动脉压力感受性反射的功能,机制与激动中枢GABAA受体有关。

Objective： To observe the effects of central gamma - aminobutyric acid （GABA） on blood pressure and baroreflex sensitivity （BRS） in conscious, freely moving spontaneously hypertensive rats （SHR）. Methods ： GABA, muscimol （ a GABAA receptor agonist）, bicuculline （ a GABAA receptor antagonist ） were dissolved into artificial cerebrospinal fluid （ ACSF ） and injected into lateral cerebral ventricles （ intracerebroventricularly, Icv ） in SHR and normotensive Wistar- Kyoto rats {WKY） as. control. Mean artery blood pressure （ MAP） was recorded in conscious, freely moving SHR and WKY. BRS was measured by the widely used method derived from that of Smyth firstly applied for human. Results ： In all of the experiments, basal MAP in SHR were already higher ,but BRS lower in SHR than in WKY. Compaired with Icv injection of ACSF（ 10μl）,Icv injection of GABA [10μmol （10μl） ] in SHR significantly decreased MAP and increase BRS. Moreover,the changes of both MAP and BRS after the administration of GABA in SHR were more remarkable than in WKY. So did with Icv injection of muscimol. Howere, MAP significantly increased and BRS decreased after Icv bicuculline （ 3 nmol ） in SHR and WKY. Also, the changes of MAP （ without BRS ） was more remarkable in SHR than in WKY. Conclusion Tbese results suggest that, in conscious, freely moving SHR, GABA has an antihypertensive effect and can improve BRS . This may be due to its activating central GABAA receptor.