Effect of ramipril on the regulation of the expression of connexins             40 and 43 in a rabbit model of arterial balloon injury.
Gap junctions (GJs) between the cells play a pivotal role in the transformation             and proliferation processes of vascular smooth muscle cells (VSMCs). However,             the expression of the component proteins of GJs, connexins 40 and 43 (Cx40 and             Cx43), are inconsistent in numerous cases. The aim of this study was to determine             whether Cx40 and Cx43 play different roles in the renin-angiotensin system (RAS)             involved in the remodeling of GJs in VSMCs under pathological conditions. A total             of 28 male New Zealand white rabbits were divided medially into four groups: control,             sham injury, injury and injury plus ramipril (0.5 mg/kg/day in the diet for two             weeks). The animals were used to set up the rabbit model of arterial balloon injury.             Transmission electron microscopy, western blotting, immunohistochemistry and reverse             transcription‑polymerase chain reaction (RT-PCR) were performed on four samples             of ballooned iliac arteries. Larger and more abundant GJs appeared in neointimal             VSMCs and there were smaller and fewer GJs following ramipril treatment. mRNA             and protein expression levels and level of immunostaining of Cx40 and Cx43 were             consistently increased following injury. Although ramipril reduced the change             in the levels of Cx43, no significant changes in Cx40 immunostaining, protein             or mRNA levels were observed in the ramipril treatments. Ramipril may inhibit             neointimal formation and downregulate the expression of Cx43 protein and mRNA,             but the drug had no significant effect on the Cx40 protein and mRNA levels, suggesting             that it was not Cx40 but Cx43 in GJs that contributes to the process of angiotensin II             (Ang II)-converting enzyme inhibitors inhibiting the prolife-ration of VSMCs in             balloon injury.
Department of Integrated Internal Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
De-Qiang
DQ
Li
Wei-Xing
WX
Chen
Yu-Ping
YP
Zhou
Yang
Y
Han
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002404:Catheterization; D049109:Cell Proliferation / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D017629:Gap Junctions / Q000378:metabolism; D007083:Iliac Artery / Q000293:injuries* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D058426:Neointima / Q000517:prevention & control; D011817:Rabbits; D017257:Ramipril / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000097003:Gap Junction alpha-5 Protein
D000806:Angiotensin-Converting Enzyme Inhibitors; D018031:Connexin 43; D017630:Connexins; D017257:Ramipril; D000097003:Gap Junction alpha-5 Protein