Effects of phosphodiestrase type 5 inhibitors in epinephrine-induced arrhythmia in rats: Involvement of lactate dehydrogenase and creatine kinase downregulation and adiponectin expression

Abstract

Cardiac arrhythmia is a common cause of mortality, and its progression may be due to abnormal sympathetic nerve activity and catecholamine release. Besides, lactate dehydrogenase (LDH) and creatine kinase (CK) downregulation and adiponectin expression play important roles in promoting coronary artery disease. The study aimed to examine the possible cardioprotective effect of members of phosphodiesterase type 5 (PDE-5) inhibitors in epinephrine-induced arrhythmia in rats. Arrhythmia was induced by cumulative boluses of epinephrine (4, 8, 16, 32, 64, and 128 mg/kg) given at 10-min intervals. Rats were randomly allocated into five groups. Group I: Normal control group received only saline. Group II: Rats injected with epinephrine and served as arrhythmia group. Groups III, IV, and V: Rats received daily oral sildenafil (0.5 mg/kg), vardenafil (3 mg/kg), and tadalafil (10 mg/kg), respectively, for 30 days prior to epinephrine injections. Injection of epinephrine to rats decreased heart rate and QTc interval but increased RR interval and duration of arrhythmia. Epinephrine group had lower serum reduced glutathione (GSH) and adiponectin levels and higher serum malondialdehyde (MDA), nitric oxide (NO), heart LDH, and CK contents. Histopathological investigations of epinephrine group provoked necrotic changes with strong positive immunoreactivity for caspases-3. While pretreatment of rats with PDE-5 inhibitors improved GSH and adiponectin contents, ameliorated serum MDA and NO levels and heart LDH and CK contents and corrected epinephrine-induced histopathological changes. PDE-5 inhibitors may delay epinephrine-induced arrhythmia through expression of adiponectin and downregulation of heart LDH and CK.

Cardioprotective effect of thymol against adrenaline-induced myocardial injury in rats

“…Subcutaneous administration of adrenaline (2 mg/kg) for 2 consecutive days in the present study resulted in abnormalities in ECG pattern as manifested by prolongation of RR interval, decrease in HR, and elevation in ST interval. This finding is in harmony with that of Salama et al. (2018) and indicates the induction of myocardial damage by adrenaline.…”

“…In the same manner, adrenaline administration significantly reduced Bcl2 protein expression and elevated caspase-3 protein expression as compared to normal rats, showing that adrenaline-induced MI was mediated by apoptosis. This finding is inaccordance with that of Salama et al. (2018) .…”

“…Rats were anesthetized with thiopental (45 mg/kg, i.p.). ECG was recorded for 1 min by inserting subcutaneous peripheral limb electrodes using ECG Powerlab module that consists of Powerlab/8sp, and animal bio-amplifier, Australia, in addition to Lab Chart7 software with ECG analyzer ( Salama et al., 2018 ). Heart rate (HR), RR interval, and ST height were recorded.…”

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

“…The blood was allowed to flow into a clean dry centrifuge tube and left to stand 30 min before centrifugation to avoid hemolysis. Then blood samples were centrifuged for 15 min at 3000 rpm [30][31][32]. and the clear supernatant serum was separated then collected by Pasteur pipette into a dry clean tube to use for determination of serum levels of glucose, TAC, α-amylase, TC and HDL-C according to [33][34][35].…”

C-Phycocyanin isolated from Microcystis aeruginosa Kützing mitigates renal injury induced by potassium dichromate via toll-like receptor-4 down regulation in rats

“…The tissue sections were stained with hematoxylin and eosin and observed under the light microscope. The slides were observed for histopathological changes and microphotographs were taken using a microscope system (Olympus, Japan) [34].…”