环鸟苷酸依赖的蛋白激酶对心血管功能的调节作用

环鸟苷酸(cGMP)依赖的蛋白激酶(PKG)是一氧化氮-cGMP的主要细胞内受体,在哺乳动物细胞中分为PKG-I和PKG-II两型。在PKG介导的血管平滑肌舒张作用中,其主要通过活化细胞膜上的钙活化的钾通道(BK通道),磷酸化肌质网上的受磷蛋白(phospholamban,PLB)和三磷酸肌醇受体相关的PKG-I底物(IP3receptor-associated PKG-I substrate,IRAG),降低细胞内Ca2 浓度。PKG还可通过活化肌球蛋白轻链磷酸酶及抑制Rho激酶降低肌球蛋白对Ca2 敏感性。PKG调节血管平滑肌细胞的基因表达和表型调变,调节细胞增生。PKG活化以后还具有抑制血小板聚集,抑制心肌细胞肥大等功能。最近的研究证明,PKG的表达水平和活性改变与动脉粥样硬化和再狭窄、高血压、糖尿病心血管病变以及硝酸盐耐受等的发病机制有密切关系。

Role of cGMP-dependent protein kinase in the cardiovascular system

cGMP-dependent protein kinase(PKG) is the major intracellular receptor for cyclic guanosine monophosphate(cGMP).Two forms of PKG,PKG-I and PKG-II,occur in mammalian tissues.PKG may mediate nitric oxide-cGMP-induced vasodilation through decreasing intracellular calcium concentration by the activation of calcium-activated potassium channel on the cell membrane and phosphorylation of phospholamban(PLB) and IP_3 receptor-associated PKG-I substrate(IRAG) on the sarcoplasmic reticulum.PKG may also decrease the sensitivity of myosin to calcium by stimulating the activity of myosin light chain phosphatase and by inhibiting Rho kinase activity.PKG plays an important role in regulating the gene expression,phenotype,and proliferation of vascular smooth muscle cells.PKG activation inhibits platelet aggregation and myocardial hypertrophy.Recent studies indicate that the alternations of PKG expression and activity are closely related with the pathogenesis of atherosclerosis,restenosis,hypertension,hyperlipemia as well as nitrate tolerance.