Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

Abstract

Objectives:: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Methods:: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). Results:: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. Conclusions:: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

“…Also, Bakovic et al [46] demonstrated that the increased sympathetic nerve fiber density in diabetic hearts started 2 weeks after induction of DM and reaching its peak after 2 months, then declined 6 to 12 months after DM induction. Also, a recent study by Hussein and colleagues demonstrated similar findings [9]. Moreover, we found in the current work a significant reduction in TH density and myocardial NE contents by either SGLT2i or GLP1, suggesting attenuation of the sympathetic nerve fiber activity is another possible mechanism for the cardioprotective effects of these new antidiabetic agents in DCM.…”

“…Therefore, strategies aiming to modulate fibrosis, inflammation, apoptosis and oxidative stress could be effective in management of DCM. Also, a recent study reported a significant increase in sympathetic nerve endings density (by measuring tyrosine hydroxylase activity) in the hearts of type 2 diabetic rats [9].…”

Short-Period Temporal Dispersion Repolarization Markers Predict 30-Days Mortality in Decompensated Heart Failure

“…Of note, besides the direct myocardial structural damages (i.e., ischemia, necrosis, fibrosis, hypertrophy, disarray, etc.) [ 5 , 6 ], drugs [ 7 , 8 , 9 ], aging [ 9 , 10 , 11 , 12 ], mental stress [ 13 , 14 , 15 ] and neurohumoral activation [ 4 , 10 , 12 , 16 , 17 , 18 , 19 , 20 , 21 ], as well as the immune–inflammatory response [ 22 , 23 ] are all factors able to worsen the myocardial repolarization phase. Thus, due to the abovementioned high susceptibility to different possible stressors, there is growing interest in the analysis of myocardial repolarization phase dispersion as a possible marker of global cardiovascular risk rather than a mere non-invasive electrophysiological marker of electrical instability.…”

<p>SGLT2 Inhibitors: A Novel Player in the Treatment and Prevention of Diabetic Cardiomyopathy</p>

“…Studies have shown that the density and number of sympathetic nerve fibers are significantly increased in diabetic hearts, suggesting overactivation of sympathetic nerves playing an important role in DCM. 131,132 Overactivation of the sympathetic nervous system promotes cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction. 133 Dapagliflozin decreases tyrosinehydroxylase density and myocardial norepinephrine content, contributing to attenuation of myocardial damage and fibrosis, indicating that improved sympathetic nerve activity is a potential mechanism for the cardiac protection of SGLT2Is in DCM.…”