Prevention of autologous vein graft restenosis by smearing valsartan on the vessel adventitia:the experiment with rabbits

Objective To evaluate the possibility of smearing valsartan locally on the testing vessel in the management of vein graft failure and to investigate the mechanism.Methods Rabbit models of jugular veins grafted into the common carotid arteries were established.Animals were randomly divided into pluronic-F-127 gel group(smearing pluronic-F-127 gel on the adventitia of autologous vein grafts)and valsartan group(smearing valsartan mixed with pluronic-F-127 gel on the adventitia of autologous vein grafts).Seven days,fourteen days and twenty-eight days after the operation,proliferating cell nuclear antigen(PCNA)were localized by immunohistochemical procedure.Fourteen days after the operation,the thickness of neointima,media and neointima/media ratios(I/M)were calculated from the sections stained with HE and Masson by computer image analysis.Fourteen days after the operation,angiotensin II type 2 receptor mRNA expressions was assayed with RT-PCR analysis.Results Fourteen days after the operation,the thickness of neointima,media and I/M ratios in valsartan group were significantly less than those of pluronic-F-127 gel group;the mRNA of AT2 receptor expressed significantly higher than that in pluronic-F-127 gel group.Seven days,fourteen days and twenty-eight days after the operation,the proliferating rate of vascular smooth muscul cell in valsartan group decreased significantly than those in pluronic-F-127 gel group.Conclusions Smearing valsartan mixed with the pluronic-F-127 gel on the autologous vein grafts can inhibit the proliferation of VSMC,which alleviated the hyperplasia of both neointima and media.The mechanism may be associated with the expression of up-regulation of AT2 receptor mRNA in the wall of local veins.These results highlight the potential therapeutic benefit in treating vein graft failure.