Impact of prolonged nicotine administration on myocardial function and susceptibility to ischaemia‐reperfusion injury in rats

• Published in: Basic & clinical pharmacology & toxicology Vol. 128; no. 2; pp. 322 - 333
• Main Authors: Ramalingam, Anand, Mohd Fauzi, Norsyahida, Budin, Siti Balkis, Zainalabidin, Satirah
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2021
• Subjects: Animals; Coronary Circulation - drug effects; Cyclosporine A; Disease Models, Animal; Drug Administration Schedule; Flow velocity; Heart; Injuries; Ischemia; Isolated Heart Preparation; Male; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondria, Heart - pathology; Mitochondrial Permeability Transition Pore - metabolism; MitoTEMPO; Myocardial Reperfusion Injury - chemically induced; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Nicotine; Nicotine - administration & dosage; Nicotine - toxicity; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - toxicity; Permeability; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion; Rodents; Superoxide Dismutase; Susceptibility; Ventricle; Ventricular Function, Left - drug effects; Cyclosporine A; MitoTEMPO; Mitochondria; Nicotine; Superoxide Dismutase
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13500

This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia‐reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague‐Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end‐point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine‐administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre‐incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine‐induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS‐driven increase in mitochondrial permeability transition.