Valsartan attenuates sympathetic hyperinnervation and suppresses the inducibility of ventricular arrhythmia in rats with myocardial infarction

The mechanism whereby valsartan (Val) decreases the incidence of programmed electrical stimulation (PES)-induced ventricular arrhythmia following myocardial infarction (MI) is still not fully understood. The article examined the sympathetic and parasympathetic nerve remodeling along the border of infarction (BZ) after the infarction and found the influence of valsartan on the remodeling process and their connection with post-infarction ventricular arrhythmias. The Sprague-Dawley male adult rats (n = 60) were randomly allocated to 3 groups viz., the sham-operated (n = 20), myocardial infarction control (CON; n = 20), and valsartan-treated ( Val; 20 mg/kg/day by oral gavage, n = 20). Electrophysiological parameters, cardiac performance, and frequency of PES-induced ventricular arrhythmias were also compared across groups eight weeks following MI induction. Histological and molecular analyses of blood and myocardial tissues were done. ELISA was used to measure the serum contents of epinephrine (EPI) and angiotensin II (ANG II) and immunofluorescence staining was used to measure the expression of growth-associated protein 43 (GAP43) and tyrosine hydroxylase (TH). Ventricular tachycardia (VT) was found to be inducible by PES in 10 (1/20) sham group, 57.14 (8/14) CON group, and 18.75 (3/16) Val group. In line with this, the scores of arrhythmia were 0.48 + 0.50, 1.70 + 0.65, and 1.04 + 0.66 in sham, CON, and Val, respectively. Valastartan group scored significantly lower on arrhythmia as compared to the CON group (P = 0.012). There was a significant reduction of EPI and ANG II of the myocardial border edema in valsartan treated rats than in the controls (7.31 ± 1.25 µg/g protein vs. 12.54 ± 1.51 µg/g protein and 11.68 ± 1.32 µg/g protein, respectively; P < 0.001 in both cases). The difference in the presence of GAP43- and TH-positive nerve fibers in the Val group and the CON group was observed using immunofluorescence and showed the changes. The density of GAP43 and TH-positive neurons in the Val group was found to be lower in comparison with the CON group. Specifically, the mean GAP43 protein expression level in the Val group was significantly lower than that in the CON group (0.057 ± 0.021 vs. 0.084 ± 0.036 and 0.080 ± 0.032, P = 0.015 and 0.029). Furthermore, the TH protein expression level in the Val group was lower than that in the CON group as well (0.03 ± 0.01 vs. 0.17 ± 0.05 and 0.22 ± 0.07, P = 0.026 and 0.046). Subsequent to myocardial infarction, the myocardial tissue has been shown to exhibit a significant decrease in mRNA and protein expression of TH in the brainstem. However, valsartan has been observed to have the capacity to enhance TH expression. Valsartan has been demonstrated to modulate myocardial reinnervation in the aftermath of myocardial infarction.These results suggest that valsartan suppresses the post-MI sympathetic hyper-reinnervation, which will decrease the risk of experiencing the ventricular arrhythmia caused by PES.