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降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用
引用本文:WuDM ZwiePA. 降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用[J]. Acta pharmacologica Sinica, 2001, 22(7): 588-594
作者姓名:WuDM ZwiePA
作者单位:[1]CardiovascularResearch,BoehringerIngelheimPharmaKG,BirkendorferStr65,d-88397Biberach,Germany [2]DepartmentofPharmacotherapy,AcademicMedicalCentre,UniversityofAmsterdam,Meibergdreef15,1105
摘    要:INTRODUCTION Calcitonin gene-related peptide (CGRP) is a 37amino acid peptide that is predominantly synthesized andstored in sensory neurons. It can be released from boththe central and peripheral axons of these neurons.CGRP-containing nerve fibers have been identifiedthroughout the cardiovascular system, in association withblood vessels, in particular the coronary arteries, andaround the sinoatrial and atrioventricular nodes.CGRP is a potent vasodilator peptide and it exerts positivechronotropic and inotropic effects in rats and hu-mans. It has been shown to exert extremely potent

关 键 词:降钙素基因相关肽 BIBN4096BS 心肌梗死 再灌注损伤

Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats
Dong-Mei WU,Pieter A van ZWIETEN,Henri N DOODS. Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats[J]. Acta pharmacologica Sinica, 2001, 22(7): 588-594
Authors:Dong-Mei WU  Pieter A van ZWIETEN  Henri N DOODS
Affiliation:Cardiovascular Research, Boehringer Ingelheim Pharma KG, Birkendorfer Str 65, D-88397 Biberach, Germany.
Abstract:AIM: The cardioprotective effect of calcitonin gene-related peptide (CGRP) was investigated in an ischemia rat model. METHODS: Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlusion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the infarct area. Plasma creatine phosphokinase levels were determined by means of a creatine phosphokinase (CPK) kit. A radioimmunoassay was used to determine plasma CGRP levels. RESULTS: Intravenous infusion of CGRP (1 nmol . kg-1 . h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 %+/- 5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase. Infusion of the same dose of CGRP commencing from the start of reperfusion until its end induced a 40 % +/- 3 % reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CG RP antagonist BIBN4096BS (20 nmol . kg-1 . h-1). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventricle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size. CONCLUSION: The present study demonstrates that CGRP is a potent myocardial protective substance.
Keywords:calcitonin gene-related peptide  BBN4096BS  myocardial infarction  reperfusion injury
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