Downregulation of Angiotensin II type 1 Receptor and GRK5 in the PVN of Heart Failure Animals Following Exercise Training

Although Exercise Training (ExT) is an important therapeutic strategy for improving quality of life in patients with chronic heart failure (CHF), the central mechanisms by which ExT is beneficial are not well understood. Angiotensin II type 1 Receptor (AT1R) plays a pivotal role in the revelation of heart failure, and as such is upregulated in a number of tissues. AT1R and other G Protein Coupled Receptors are marked for internalization and recycling via G Protein Coupled Receptor Kinase (GRK) phosphorylation. Because previous studies have shown that the beneficial effects of ExT rely on a reduction in Ang II, we hypothesized ExT would decrease AT1R expression and the regulation of AT1R by GRK5 in the Paraventricular Nucleus (PVN) of infarcted rats. Animals were infarcted using coronary artery ligation and were exercised four weeks post‐surgery on a treadmill at a final speed of 25 m/min for 60 minutes, 5 days a week for six weeks. Western blot analysis of PVN revealed a significant (p<0.003) upregulation of both AT1R and GRK5 in the infarcted group, a trend that was reversed by ExT (p<0.03). Furthermore, the relative expression of phosphorylated AT1R and AT1R/GRK5 physical association was increased in the infarcted sedentary group, and reversed by ExT. Taken together, increased GRK5 may serve as a compensatory mechanism for AT1R upregulation in HF, and ExT mitigates the increase in both AT1R and its regulatory components.