Hypertension is one of the most common cardiovascular diseases that seriously endangers human health and has become a significant public health problem worldwide. In the vast majority of patients, the cause of hypertension is unknown, called essential hypertension (EH), accounting for more than 95% of total hypertension. Epidemiological and genetic studies of humans and animals provide strong evidence of a causal relationship between high salt intake and hypertension. Adducin is one of the important candidate genes for essential hypertension. Adducin is a heterodimeric or heterotetrameric protein that consists ofα,β, andγsubunits; the three subunits are encoded by genes (ADD1,ADD2, andADD3) that map to three different chromosomes. Animal model experiments and clinical studies suggest that changes in single-nucleotide polymorphisms (SNPs) at part of the adducin family gene increase the Na⁺-K⁺-ATPase activity of the renal tubular basement membrane and increase the reabsorption of Na⁺by renal tubular epithelial cells, which may cause hypertension. This review makes a summary on the structure, function, and mechanism of adducin and the role of adducin on the onset of EH, providing a basis for the early screening, prevention, and treatment of EH.

Background: Sacubitril/valsartan (SAC/VAL), combined inhibitors of angiotensin receptor (AT-R) and neprilysin receptor, prevents Angiotensin Ⅱ (AngⅡ) from binding AT₁-R and blocks degradation of natriuretic peptides. Despite its efficacy in reducing ventricular fibrosis and preserving cardiac functions, which has been extensively demonstrated in myocardial infarction or pressure overload models, few studies have been conducted to determine whether SAC/VAL could attenuate atrial fibrosis and decrease atrial fibrillation (AF) susceptibility. Methods: Sprague-Dawley rats were divided into three groups after implantation of an osmotic pump preloaded with AngⅡ and received corn oil, VAL, or SAC/VAL treatment for 28 days. Electrophysiological study was performed to determine inducibility and duration of AF. Echocardiography was performed before and 28 days after osmotic mini-pump implantation to evaluate cardiac functions. Enzyme-linked immunosorbent assay was perfomed to detect the serum concentration of atrial natriuretic peptide (ANP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and AngⅡ. Masson staining was performed to determine the extent of interstitial fibrosis. Immunohistochemical, and immunofluorescence staining as well as transwell and MTT assay were also performed. Western blot analysis was perfomed to figure out how SAC/VAL exerts its anti-fibrosis effects in atriums.Results: After 28 days of AngⅡ stimulation, rats in SAC/VAL group exhibited reduced reduced extent of atrial fibrosis, inhibited proliferation, migration, and differentiation of atrial fibroblasts and decreased susceptibility to atrial fibrillation. We further found that SAC/VAL exerted its effect on AngⅡ-induced atrial fibrosis by inhibiting the p-Smad2/3, p-JNK, and p-p38 MAPK signaling pathways in vivo. Conclusions: Our study provided experimental evidence for the inhibition of atrial fibrosis and reduced susceptibility to AF by SAC/VAL. These results emphasize the importance of SAC/VAL in the prevention of AngⅡ-induced atrial fibrosis and may help to enrich the options for atrial fibrillation pharmacotherapy.