Kininase-independent potentiation of endothelium-dependent relaxations to kinins by converting enzyme inhibitor perindoprilat  

转换酶抑制剂培哚普利拉非激肽酶依赖性地加强由激肽引起的内皮依赖性血管松弛(英文)

作　　者：Jean Vivien MOMBOULI Kevin D BALLARD Paul M VANHOUTTE 

机构地区：[1]Center for Experimental Therapeutics,Baylor College of Medicine,Houston,Texas,USA [2]Institut de Recherches Internationales Servier,92415 Courbevoie Cedex,France

出　　处：《Acta Pharmacologica Sinica》2002年第3期15-19,共5页中国药理学报（英文版）

摘　　要：The present study examined whether or not the resistance to degradation of bradykinin analogs affects the kinin-potentiating action of the inhibitor of converting enzyme, perindoprilat. METHODS: Hydrolysis of [Hyp3,Tyr(Me)8]-bradykinin by ACE present in isolated canine coronary arteries was assessed by determination of peptide metabolites using electrospray mass spectrometry, and compared to that of bradykinin. Contractions and relaxations of isolated rings of coronary arteries, with and without endothelium, were recorded as changes in isometric force. RESULTS: After a 30 min incubation, most of the bradykinin was degraded by the arteries, while less than 10 % of [Hyp3 Tyr(Me)8]-bradykinin was hydrolysed. In organ chambers, [Hyp3, Tyr(Me)8]-bradykinin like bradykinin caused relaxations of isolated canine coronary arteries with endothelium that could be attributed to both NO and endothelium-derived hyperpolarizing factor (EDHF). Perindoprilat caused a comparable leftward shift in the concentration-relaxation curves for bradykinin and [Hyp3,Tyr(Me)8]-bradykinin. CONCLUSION: Impairment of the degradation of bradykinin is not an essential mechanism by which perindoprilat potentiates the actions of kinins.The present study examined whether or not the resistance to degradation of bradykinin analogs affects the kinin-potentiating action of the inhibitor of converting enzyme, perindoprilat. METHODS: Hydrolysis of [Hyp3,Tyr(Me)8]-bradykinin by ACE present in isolated canine coronary arteries was assessed by determination of peptide metabolites using electrospray mass spectrometry, and compared to that of bradykinin. Contractions and relaxations of isolated rings of coronary arteries, with and without endothelium, were recorded as changes in isometric force. RESULTS: After a 30 min incubation, most of the bradykinin was degraded by the arteries, while less than 10 % of [Hyp3 Tyr(Me)8]-bradykinin was hydrolysed. In organ chambers, [Hyp3, Tyr(Me)8]-bradykinin like bradykinin caused relaxations of isolated canine coronary arteries with endothelium that could be attributed to both NO and endothelium-derived hyperpolarizing factor (EDHF). Perindoprilat caused a comparable leftward shift in the

关 键 词：bradykinin receptors nitric oxide ENDOTHELIUM angiotensin-converting enzyme inhibitors peptidyl-dipeptidase A 

分 类 号：R96[医药卫生—药理学]