Ming-Sheng Zhou
Liaoning Medical University, China
Title: Role of Ang II activation of NFkB in development of endothelial dysfunction and skeletal muscle insulin resistance in salt-sensitive hypertension
Biography
Biography: Ming-Sheng Zhou
Abstract
Insulin resistance is highly prevalent in patients with essential hypertension, particularly those with salt-sensitivity (SS), and frequently progress to type II diabetes and cardiovascular diseases (CVD). However, there are still critical gaps in our knowledge of the mechanisms that lead to the development of insulin resistance in SS hypertension. Recent studies have underscored the importance of heightened activation of the renin-angiotensin system, oxidative stress and inflammation in promoting insulin resistance and CVD. Using Dahl SS rat, a paradigm of human SS hypertension characterized by CVD and insulin resistance, we have demonstrated that in SS hypertension, despite low plasma renin levels, there is an upregulation of local Ang II action that contributes to increased NADPH oxidase-derived ROS production and activation of NFï«B associated with impaired insulin activation of phosphatidylinositol 3-kinase (PI3K) signaling pathway in the vasculature and skeletal muscle. Furthermore, we have shown that treatment with angiotensin receptor 1 blocker candesartan, antioxidant tempol or NFï«B inhibitor PTDC improved endothelial function, vascular injury and insulin signaling molecules through PI3K pathway, reduced ROS production and NFï«B activation in the vasculature and skeletal muscle. PCR array showed that eight genes among 84 target genes related to obesity, insulin resistance and inflammation were altered in the soleus muscle of hypertensive rats, which were reversed by specific peptide inhibitor of NFï«B SN50. These results suggest that activation of the NFï«B inflammatory pathway by endogenous Ang II-ROS plays critical role in the development of endothelial dysfunction, skeletal muscle insulin resistance in SS hypertension.