Effects of the L/N-Type Ca²⁺ Channel Blocker Cilnidipine on the Cardiac Histological Remodelling and Inducibility of Atrial Fibrillation in High-Salt-Fed Rats

Abstract

High salt intake has been shown to induce hypertrophy and fibrosis in the atria and ventricles, which could result in the development of atrial fibrillation (AF). Whereas the development of AF is suggested to be prevented by renin-angiotensin system (RAS) inhibitors, recent findings have indicated that this prevention is closely associated with their antihypertensive effects. In this study, we investigated whether the L/N-type Ca 2 channel blocker cilnidipine counteracts salt-induced atrial and ventricular remodelling and the inducibility of AF. Cilnidipine was orally administered to Dahl salt-sensitive rats fed with an 8% NaCl diet at 10 mg/kg for 5 weeks, and then electrophysiological evaluation and histological analyses were performed. The effects were compared with those of the L-type Ca 2 channel blocker amlodipine at 3 mg/kg. Following the intake of the 8% NaCl diet, the blood pressure (BP) increased, and fibrosis was induced in the atria and ventricles. Cilnidipine decreased BP, and the extent of the decrease in the cilnidipine group was similar to those in the amlodipine group. Cilnidipine produced a greater decrease in the fibrotic area in the atria and ventricles than amlodipine. The cilnidipine group shortened the AF duration from 7.43 3.16 to 2.95 1.73 s, which had been increased by NaCl intake. Plasma noradrenaline levels in the cilnidipine group were lower than those in the amlodipine group. Thus, the suppressive effects of cilnidipine on the salt-induced atrial and ventricular remodelling, fibrosis, and AF sustainability might be closely associated with its N-type Ca 2 channel-blocking actions.

Evaluating the association between dietary salt intake and the risk of atrial fibrillation using Mendelian randomization

“…Recently, Li et al found that excess dietary salt intake was related to myocardial remodeling, as well as the impairment of cardiac function and myocardial viability, and inflammation perhaps plays a role in these relationships ( 37 ). Previous research also found that high salt intake was correlated with cardiomyocyte hypertrophy, interstitial fibrosis, and cardiac dysfunction ( 38–40 ). Lader et al found that a salt-induced increase in blood pressure could lead to the activation of the K ATP channel and thus increased arrhythmia inducibility ( 41 ).…”

“…Lader et al found that a salt-induced increase in blood pressure could lead to the activation of the K ATP channel and thus increased arrhythmia inducibility ( 41 ). A recent study by Harada et al found that QRS and QT intervals were prolonged and AERP shortened in Dahl rats fed a high-salt diet ( 38 ). Meanwhile, a growing body of evidence suggests the correlation between salt intake and the rennin-angiotensin-aldosterone system, which plays a critical role in the development of AF ( 42–44 ).…”