Silencing salusin β ameliorates heart failure in aged spontaneously hypertensive rats by ROS-relative MAPK/NF-κB pathways in the paraventricular nucleus

Abstract

ObjectiveSustained hypertension is a major cause of heart failure in aging hypertensive patients. Salusin β, a novel bioactive peptide of 20 amino acids, has been reported to participate in various cardiovascular diseases, including hypertension. We therefore hypothesized that central knockdown of salusin β might be effective for hypertension-induced heart failure treatment. Methods and resultsEighteen-month-old male aged spontaneously hypertensive rats (SHR) with heart failure and WKY rats were microinjected with either a specific adenoviral vector encoding salusin β shRNA (Ad-Sal-shRNA) or a scramble shRNA (Ad-Scr-shRNA) in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. Radiotelemetry and echocardiography were used for measuring blood pressure and cardiac function, respectively. Blood samples and heart were harvested for evaluating plasma norepinephrine, tyrosine hydroxylase, and cardiac morphology, respectively. The mesenteric arteries were separated for measurement of vascular responses. The PVN was analyzed for salusin β, proinflammatory cytokines (PICs), mitogen-activated protein kinase (MAPK), NF-κB, and reactive oxygen species (ROS) levels. Compared with normotensive rats, aging SHR with heart failure had dramatically increased salusin β expression. Silencing salusin β with Ad-Sal-shRNA attenuated arterial pressure and improved autonomic function, cardiac and vascular dysfunction in aging SHR with heart failure, but not in aging WKY rats. Knockdown of salusin β significantly reduced paraventricular nucleus PICs levels, MAPK and NF-κB activity, and ROS levels in aging SHR with heart failure. ConclusionThese data demonstrate that in aging SHR, the heart failure that was developed during the end stage of hypertension could be ameliorated by silencing salusin β.