Activation of protein kinase A improves vascular endothelial dysfunction.
Activation of protein kinase A improves vascular endothelial dysfunction.
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蛋白激酶 A 的激活可改善血管内皮功能障碍。
DOI：
10.1080/10623320600904047
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Singh,Manjeet
中科院分区：
文献类型：
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作者：
Shah,DhvanitI;Singh,Manjeet
本研究旨在研究蛋白激酶A（PKA）激活剂8-Br-cAMP在糖尿病和高同型半胱氨酸血症诱导的血管内皮功能障碍中的作用。链脲佐菌素（55 mg kg−1，i. v.）和甲硫氨酸（1.7%w/w，p.o.，4周）分别给予大鼠以产生糖尿病（血清葡萄糖>200 mg dL-1）和高同型半胱氨酸血症（血清同型半胱氨酸>10 μM）。采用离体主动脉环制备、胸主动脉电子显微镜检查和血清亚硝酸盐/硝酸盐浓度评估血管内皮功能障碍。逆转录聚合酶链反应（RT-PCR）检测p22 phox和内皮型一氧化氮合酶（eNOS）mRNA的表达。血清硫代巴比妥酸反应物质（TBARS）浓度和主动脉超氧阴离子浓度估计氧化应激。8-Br-cAMP（5 mg kg−1，i.p.）或阿托伐他汀（30 mg kg−1，p.o.）预防糖尿病和高同型半胱氨酸血症引起的乙酰胆碱诱导的内皮依赖性舒张的衰减、血管内皮衬里的损伤、eNOS mRNA表达的降低、血清亚硝酸盐/硝酸盐浓度以及p22 phox、超氧阴离子和血清TBARS mRNA表达的增加。N ω-硝基-L-精氨酸甲酯（L-NAME）（25 mg kg−1，i. p.）和格列本脲（5 mg kg-1，i. p.）。因此，可以得出结论，8-Br-cAMP诱导的PKA活化可以改善血管内皮功能障碍。
The study has been designed to investigate the effect of 8-Br-cAMP, an activator of protein kinase A (PKA), in diabetes mellitus– and hyperhomocysteinemia-induced vascular endothelial dysfunction. Streptozotocin (55 mg kg−1, i.v.) and methionine (1.7%w/w, p.o., 4 weeks) were administered to rats to produce diabetes mellitus (serum glucose >200 mg dL−1) and hyperhomocysteinemia (serum homocysteine >10 μM), respectively. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta, and serum concentration of nitrite/nitrate. The expression of mRNA for p22phox and endothelial nitric oxide synthase (eNOS) was assessed by using reverse transcriptase–polymerase chain reaction (TBARS) (RT-PCR). Serum thiobarbituric acid–reactive substances (TBARS) concentration and aortic superoxide anion concentration were estimated to assess oxidative stress. 8-Br-cAMP (5 mg kg−1, i.p.) or atorvastatin (30 mg kg−1, p.o.) prevented diabetes mellitus– and hyperhomocysteinemia-induced attenuation of acetylcholine-induced endothelium-dependent relaxation, impairment of vascular endothelial lining, decrease in expression of mRNA for eNOS, serum nitrite/nitrate concentration, and increase in expression of mRNA for p22phox, superoxide anion, and serum TBARS. The ameliorative effect of 8-Br-cAMP was prevented byNω-nitro-L-arginine methyl ester (L-NAME) (25 mg kg−1, i.p.) and glibenclamide (5 mg kg−1, i.p.). Therefore, it may be concluded that 8-Br-cAMP–induced activation of PKA may improve vascular endothelial dysfunction.