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

作者：Xu, Yu; Fei, Xuejie; Fu, Hangjiang; Chen, Aidong; Zhu, Xinrui; Zhang, Feng; Han, Ying^*

来源：Acta Physiologica, 2023, 238(4).

DOI：10.1111/apha.13987

• cardiac sympathetic afferent reflex
• chronic heart failure
• paraventricular nucleus
• reactive oxygen species
• sympathetic activity
• TOR2A gene product

AimEnhanced cardiac sympathetic afferent reflex (CSAR) promotes sympathetic hyperactivation in chronic heart failure (CHF). Salusin-beta 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-beta 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. MethodsCSAR 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. ResultsSalusin-beta protein expression was upregulated in the PVN of the CHF compared with sham-operated rats. Salusin-beta microinjection into the PVN dose-dependently increased MAP and RSNA and enhanced CSAR, while anti-salusin-beta IgG exerted opposite effects. The effect of salusin-beta 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-beta IgG was interdicted by nitric oxide (NO) synthase inhibitor. Furthermore, chronic salusin-beta 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. ConclusionIncreased salusin-beta 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-beta expression might be a novel strategy for preventing and treating CHF in the future.

• 单位
  同济大学; y