Upregulated expression of a TOR2A gene product‐salusin‐β in the paraventricular nucleus enhances sympathetic activity and cardiac sympathetic afferent reflex in rats with chronic heart failure induced by coronary artery ligation

Abstract Aim Enhanced cardiac sympathetic afferent reflex (CSAR) promotes sympathetic hyperactivation in chronic heart failure (CHF). Salusin‐β is a torsin family 2 member A (TOR2A) gene product and a cardiovascular active peptide closely associated with cardiovascular diseases. We aimed to determine the roles of salusin‐β in the paraventricular nucleus (PVN) in modulating enhanced CSAR and sympathetic hyperactivation in rats with CHF induced by coronary artery ligation and elucidate the underlying molecular mechanisms. Methods CSAR was evaluated based on the responses of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) to the epicardial administration of capsaicin in rats under anesthesia. Results Salusin‐β protein expression was upregulated in the PVN of the CHF compared with sham‐operated rats. Salusin‐β microinjection into the PVN dose‐dependently increased MAP and RSNA and enhanced CSAR, while anti‐salusin‐β IgG exerted opposite effects. The effect of salusin‐β was inhibited by reactive oxygen species (ROS) scavenger or NAD(P)H oxidase inhibitor but promoted by superoxide dismutase inhibitor. The effect of anti‐salusin‐β IgG was interdicted by nitric oxide (NO) synthase inhibitor. Furthermore, chronic salusin‐β gene knockdown in PVN attenuated CSAR, reduced sympathetic output, improved myocardial remodeling and cardiac function, decreased NAD(P)H oxidase activity and ROS levels, and increased NO levels in the CHF rats. Conclusion Increased salusin‐β activity in the PVN contributes to sympathetic hyperactivation and CSAR in CHF by inhibiting NO release and stimulating NAD(P)H oxidase‐ROS production. Reducing endogenous central salusin‐β expression might be a novel strategy for preventing and treating CHF in the future.