GRK5 overexpression in the RVLM of CHF rats improves autonomic imbalance and restores AT1R and Kv4.3 expressions (686.33)

Chronic heart failure (CHF) is characterized by an overactive Angiotensin II type 1 receptor (AT1R) signaling axis and autonomic imbalance. AT1R is regulated by its phosphorylation by G protein coupled receptor kinase 5 (GRK5). We have shown previously that AT1R and GRK5 are paradoxically increased and that Kv4.3, a potassium channel involved in neuronal excitability, is decreased in the rostral ventrolateral medulla (RVLM) of rats with CHF. We tested the hypothesis is that GRK5 overexpression in the RVLM improves autonomic imbalance and normalizes AT1R and Kv4.3 expression in CHF. CHF was induced by coronary artery ligation and confirmed by echocardiography. Following implantation of radiotelemetry transducers, two weeks of heart rate (HR), mean arterial pressure (MAP) and metabolic cage data were collected before and after either vehicle (Veh) or lentiviral GRK5 (GRK5) injection into the RVLM. HR was decreased in GRK5 rats compared to Veh (293±6 vs 316±2 bpm) while MAP was unchanged. Urine norepinephrin...