Short-Term Vagus Nerve Stimulation Improves Cardiac Function and Mitigates Myocardial Remodeling in Heart Failure Rats with Preserved Ejection Fraction

Abstract

Standard therapies for heart failure with preserved ejection fraction (HFpEF) remain controversial. Vagus nerve stimulation (VNS) can downregulate extracellular matrix (ECM) expression and improve the prognosis of patients with heart failure. In order to verify whether the positive effect of VNS on HFpEF is feasible, HFpEF model constructed by Dahl salt-sensitive rats were subjected to VNS. Thirty male Dahl salt-sensitive rats were fed a high-salt diet (inducing HFpEF) and ten were fed a low-salt diet (controls) from the age of 7 weeks old. Roughly 12 weeks later, rats with HFpEF were randomly assigned to VNS (HF-VNS group, n = 13) and sham stimulation (HF-SS group, n = 13). Age-matched controls also underwent sham stimulation (control-SS group, n = 10). Cardiac function, myocardial hypertrophy, and fibrosis were evaluated after 72 h of treatment. Heart rate and systolic blood pressure decreased in rats receiving VNS compared with untreated counterparts. In addition, both systolic and diastolic cardiac function improved concurrently. The concentration of serum brain natriuretic peptide (BNP) concentration and the mRNA and protein expression of ECM proteins in serum and tissues, including collagen type I and III, connective tissue growth factor (CTGF), and transforming growth factor-β1 (TGF-β1) in serum and in tissue (mRNA and protein expression), were remarkably downregulated by VNS. VNS improved cardiac function and mitigated myocardial remodeling in Dahl salt-sensitive rats with HFpEF, which exhibited a good clinical application prospect.