摘要
目的在尾端延髓腹外侧区(CVLM),观察外源性硫化氢对麻醉大鼠血压和心率的影响,并探讨其机制。方法雄性Sprague Dawley(SD)大鼠67只分为单纯给药(n=34)和预先给予拮抗剂(n=33)大鼠。单纯给药大鼠随机分为人工脑脊液(aCSF)组(100nL,n=6),硫氢化钠(硫化氢供体)低、中、高剂量3组(20、200、2000μmol/L,n=21,每组7例)和S腺苷蛋氨酸(SAM)组[胱硫醚-β-合成酶(CBS)激动剂,1mmol/L,n=7];预先给予拮抗剂大鼠随机分为aCSF(100nL)+硫氢化钠(200μmol/L)组(n=6)、犬尿希酸(谷氨酸受体拮抗剂,5mmol/L)+硫氢化钠(200μmol/L)组(n=7)、羟胺(CBS拮抗剂,100mmol/L)+硫氢化钠(200μmol/L)组(n=7)、格列苯脲[ATP敏感性钾通道(KATP)拮抗剂]+硫氢化钠(200μmol/L)组(n=7)和二甲基亚砜(100nL)+硫氢化钠(200μmol/L)组(n=6)。结果在CVLM区域,微量注射硫氢化钠(20、200、2000μmol/L)能够呈剂量依赖性地降低平均动脉压和心率;微量注射SAM也能明显降低平均动脉压(-22±5)mm Hg和心率(-22±5)次/min(均P<0.05)。羟胺预处理不影响硫氢化钠产生的心血管效应。犬尿希酸和格列苯脲预处理分别减弱硫氢化钠降低血压效应的40.0%和69.5%,减弱降低心率效应的33.3%和63.6%。结论 KATP通道开放机制或谷氨酸受体激动机制可能介导硫化氢在大鼠CVLM产生的心血管效应。
Objective To investigate the effects and mechanisms of hydrogen sulfide （H2S） injected within the cau- dal ventrolateral medulla（ CVLM ） on blood pressure （ BP ） and heart rates （HR） in anesthetized rats. Methods Sixty-seven male Sprague Dawley（SD） rats were randomized into hydrogen sulfide （H2S） treatment（n= 34） or an- tagonist pretreatment group（n=33 ）. H2S treatment group was further divided into the following subgroups： con- trol（arificial cerehrospinal fluid, aCSF, 100 nL, n= 6）, Sodium hydrosulfide（NaHS, a H2 S donor） at the dosages of 20, 200 or 2000 μmol/L （ n = 7 for each dosage）, and S-ademetionine（SAM） （ cystathionine-β-synthase agonist） at dosage of 1 mmol/L（n= 7）. Antagonist pretreatment control groups received Naris （200 μmol/L） combined with one of the following agents： 1% dimethyl sulfoxide or aCSF （control, 100 nL, n= 6）, kynurenic acid （glutamate re- ceptor antagonist, 5 mmol/L, n= 7）, hydroxylamine （ cystathionine-β-synthase antagonist, 100 mmol/L, n= 7 ）, or glibenclamide （KATP channel antagonist, n = 7）. Results Unilateral microinjection of NariS （20, 200 or 2000 μmol/L） into the CVLM caused transient and dose-dependent hypotension and bradycardia. Similar to NariS, mi- croinjection of SAM into the CVLM also caused significant decreases in BP （-22 ± 5） mmHg and HR （-22±5） beat/min （all P〈0. 05 ）. Pretreatment with hydroxylamine, a cystathionine-β-synthase inhibitor, could not affect the cardiovascular effects of NariS. However, pretreatment with kynurenic acid or glibenclamide, a KATP channel blocker, eliminated the BP responses induced by intra-CVLM NariS by 40% and 69.5%, HR responses 33.3% and 63.6%. Conclusion These data support the hypothesis that endogenous H2S exerts cardiovascular inhibition func- tions in the CVLM through KATPchannels opening mechanism.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2014年第5期463-467,共5页
Chinese Journal of Hypertension
关键词
硫化氢
大鼠
尾端延髓腹外侧区
血压
心率
Hydrogen sulfide
Rat
Caudal ventrolateral medulla
Blood pressure
Heart rate
