摘要
目的观察地西泮(DZP)对5-羟色胺(5-HT)诱导收缩的老年大鼠离体胸主动脉环的作用,并探讨其可能的机制。方法采用离体血管张力记录法,观察5-HT对老年大鼠离体胸主动脉环的作用及DZP的影响。结果①5-HT[(0.01～3)×10-5mol/L]对老年大鼠离体胸主动脉环具有浓度依赖性的收缩作用,血管环收缩达最大收缩50%时的药物浓度(EC50)值约为3×10-6mol/L。②在内皮完整的血管环,DZP3×10-6mol/L使5-HT诱导收缩的浓度-效应曲线的最大收缩幅度(Emax)显著降低(与溶剂对照组相比,P<0.01),但去内皮后,DZP对5-HT的缩血管作用无明显影响(P>0.05)。③一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAME)能减低DZP对5-HT诱导的缩血管作用的减弱作用(P<0.01),但环氧合酶抑制剂吲哚美辛、外周型苯二氮受体(PBR)特异性阻断剂PK11195对DZP的作用无显著影响(P>0.05)。结论 5-HT对老年大鼠离体胸主动脉环具有浓度依赖性的收缩作用。DZP能显著减弱5-HT的缩血管作用,该作用具有内皮依赖性,与内皮产生的一氧化氮有关,但与前列环素无关。DZP的作用不依赖于PBR。
Objective To investigate the action of diazepam （DZP） on 5-hydroxytryptamine-induced contractions of thoracic aorta in elderly rats and probable mechanism that underlies this action.Methods Tonometry was used to determine the effects of DZP on 5-HT induced contractions in the thoracic aortic rings isolated from elderly rats.The influences of various drugs which include NG-nitro-L-arginine methyl ester （L-NAME,10-4 mol/L）,indomethacin （10-5 mol/L） and PK11195 （10-6 mol/L） on the effects of DZP were observed.Results ① （0.01～3）×10-5 mol/L 5-HT produced a concentration-dependent contraction in isolated thoracic aorta rings of elderly rats.The EC50 of 5-HT was about 3×10-6 mol/L.② In the isolated thoracic aorta rings of elderly rats with intact endothelium,DZP （3× 10-6 mol/L） significantly attenuated the Emax of 5-HT induced vasoconstriction,compared with that of the rings not treated with DZP （P0.01）.There was no significant effect of DZP on rings with denuded endothelium （P0.05）.③ The effects of DZP （3×10-6 mol/L） on the 5-HT induced vasoconstriction was suppressed by L-NAME,a nitric oxide synthase inhibitor （P0.01）,but not by cyclooxygenase inhibitor indomethacin and PK11195.Conclusion 5-HT could produce concentration-dependent vasoconstriction in isolated thoracic aorta rings of elderly rats.DZP could attenuate the vasoconstriction effects of 5-HT in an endothelium-dependent manner.The underlying mechanisms may involve release of NO from endothelium,but not PGI2 and the peripheral benzodiazepine receptor.
出处
《中国药物与临床》
CAS
2011年第6期648-650,共3页
Chinese Remedies & Clinics
基金
山西省自然科学基金(2010011055-1)
山西省高等学校科技基金(20081013)
