中国医学科学杂志(英文版)
中國醫學科學雜誌(英文版)
중국의학과학잡지(영문판)
CHINESE MEDICAL SCIENCES JOURNAL
2003年
1期
1-8
,共8页
刘乃奎%陈光慧%王晓红%姚兴海%苏加林%李田昌%武旭东%张勇刚%汤健%唐朝枢
劉迺奎%陳光慧%王曉紅%姚興海%囌加林%李田昌%武旭東%張勇剛%湯健%唐朝樞
류내규%진광혜%왕효홍%요흥해%소가림%리전창%무욱동%장용강%탕건%당조추
endothelin%angiotensin II%calcitonin gene related peptide
Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia,we observed changes of endothelin(ET),angiotensin II(AII),calcitonin gene-related peptide(CGRP)and adrenomedullin(Adm)in plasma and aorta with radioimmunoassay and expression of hypertension-related gene(HRG-1)with semi-quantitative RT-PCR,and studied the effects of these peptides on intimal hyperplasia,intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore,in cultured cells,we studied the effects of these peptides on vascular smooth muscle cell(VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats with 3H-TdR incorporation and RT-PCR respectively. Results. After angioplasty,the levels of ET and AII in plasma and aorta significantly increased,accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty,the levels of ET in plasma and aorta increased by 69% and 124% respectively,compared with sham group(P<0.01);and the level of aortic AII increased by 80%(P< 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme(ACE)could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group,on day 3 after angioplasty,the CGRP levels in plasma and aorta increased by 64% and 89% respectively(P< 0.01)and the Adm levels in plasma and tissue increased by 129% and 102% respectively(P< 0.01). On day 10,intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima forma-tion induced by balloon aortic injury(by 66% and 79% respectively,P< 0.01). In addition,ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase(MAPK)activity,while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.Conclusions. ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.