Molecular mechanism of limbs＇ postischemic revascularization improved by perindopril in diabetic rats  

作　　者：GAO Lu YU De-min 

机构地区：[1]Key Lab of Hormones and Development, Ministry of Health [2] Hospital of Metabolic Diseases, Tianjin Medical University, Tianjin 300070, China

出　　处：《Chinese Medical Journal》2008年第21期2129-2133,共5页中华医学杂志（英文版）

摘　　要：Background Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors （ACEIs） on the reduction of blood pressure and the protection of target organs, the clinical application of this kind of drugs is very widespread. However, it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs＇ postischemic revascularization. It is of major therapeutic importance to resolve these questions. This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia, the role and related molecular mechanisms of ACEI in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： ACEI by perindopril; perindopril in combination with a nitric oxide synthase （NOS） inhibitor; perindopril in combination with bradykinin （BK）-B1 receptor （BIR） antagonist or saline. The differences of angiogenesis, the mRNA and protein expression of endothelial nitric oxide synthase （eNOS）, vascular endothelial growth factor （VEGF） and basic fibroblast （bFGF）, constitutive nitric oxide synthase （cNOS） activity and nitric oxide （NO） content were observed after treatment. Results In non-ischemic hind limbs, no significant changes in capillary density, or the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity were observed among all groups. On the contrary, in ischemic hind limbs, the capillary density in diabetic rats decreased by 27% when compared with the control rats, so did the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity （P 〈0.05）. The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to untBackground Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors （ACEIs） on the reduction of blood pressure and the protection of target organs, the clinical application of this kind of drugs is very widespread. However, it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs＇ postischemic revascularization. It is of major therapeutic importance to resolve these questions. This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia, the role and related molecular mechanisms of ACEI in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： ACEI by perindopril; perindopril in combination with a nitric oxide synthase （NOS） inhibitor; perindopril in combination with bradykinin （BK）-B1 receptor （BIR） antagonist or saline. The differences of angiogenesis, the mRNA and protein expression of endothelial nitric oxide synthase （eNOS）, vascular endothelial growth factor （VEGF） and basic fibroblast （bFGF）, constitutive nitric oxide synthase （cNOS） activity and nitric oxide （NO） content were observed after treatment. Results In non-ischemic hind limbs, no significant changes in capillary density, or the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity were observed among all groups. On the contrary, in ischemic hind limbs, the capillary density in diabetic rats decreased by 27% when compared with the control rats, so did the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity （P 〈0.05）. The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to unt

关 键 词：angiotensin-converting enzyme inhibitor limb ischemia diabetes mellitus NEOVASCULARIZATION 

分 类 号：R587.1[医药卫生—内分泌]