Evidence for a pro-apoptotic phenotype in skeletal muscle of hypertensive rats

In this report, we demonstrate that soleus muscle of spontaneously hypertensive rats (SHR) had significantly lower protein levels of apoptosis repressor with caspase recruitment domain (ARC) and X-linked inhibitor of apoptosis protein (XIAP) as well as significantly higher protein levels of second mitochondria-derived activator of caspase (Smac) and procaspase-8 compared to normotensive Wistar-Kyoto (WKY) rats. In addition, soleus muscle from hypertensive rats had significantly increased caspase-8 proteolytic enzyme activity as well as significantly elevated reactive oxygen species (ROS) generation and higher hydrogen peroxide (H₂O₂) content. There was no change in the protein levels of the antioxidant enzymes, catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD). Interestingly, ARC protein migrated at approximately 32 kDa in SHR but at 30 kDa in WKY rat muscle; possibly indicating a post-translational modification. These results demonstrate that soleus muscle of hypertensive rats display a pro-apoptotic phenotype and augmented ROS generation.