内皮素拮抗剂对大鼠硝酸甘油耐药性的影响

Effect of endothelin receptor antagonist on nitroglycerin tolerance in rats

目的 :探讨内皮素受体拮抗剂Bosentan对大鼠硝酸甘油耐药的改善作用。方法 :Wistar大鼠 2 8只 ,随机分成对照组 (C组 ,n =10 ) ,硝酸甘油组 (NTG组 ,n =6 ) ,Bosentan组 (n =6 ) ,硝酸甘油 +Bosentan组 (NTG +Bosentan组 ,n =6 )。观察各组大鼠对硝普钠 (SNP)的降压反应。用放射免疫方法测定各组血浆和血管组织的内皮素 1(ET 1)含量。结果 :NTG组大鼠对SNP的降压反应最弱 ,NTG +Bosentan组大鼠对SNP的降压反应明显强于NTG组大鼠 ,NTG +Bosentan组大鼠离体主动脉环对不同浓度SNP的舒张反应较NTG组大鼠有明显的改善。NTG +Bosentan组大鼠血浆及血管组织ET 1含量与NTG组大鼠比较差异无显著性 ,均明显高于C组大鼠。结论

Objective: To investigate whether endothelin receptor antagonist Bosentan could reduce the nitroglycerin(NTG) tolerance in rats . Methods: Twenty-eight wistar rats were divided into control group(n=10),Nitroglycerin(NTG) group(n=6), Bosentan group (n=6)and NTG+Bosentan group(n=6).The hypotensive response to sodium nitroprusside(SNP) in different group rats,and the relaxation effect of different concentrations of SNP on isolated aortic rings from different group rats were observed .The endothelin-1 (ET-1) contents of plasma and vascular tissue were measured by the radioimmuno assay method. Results: The hypotention response to SNP was significantly attenuated in NTG group,compared with control group. The hypotensive response to SNP was improved in NTG+Bosentan group, compared with NTG group .The relaxation effect of SNP on isolated rat aortic ring was obviously restored in NTG+Bosentan group,compared with NTG group. The ET-1 contents of plasma and vascular tissue were markedly increased in both NTG+Bosentan group and NTG group compared with control group. Conclusion: Endothelin receptor antagonist Bosentan can prevent against the NTG tolerance .