Effect of ramipril on the regulation of the expression of connexins 40 and 43 in a rabbit model of arterial balloon injury.
ABSTRACT 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.