Mito‐targeted antioxidant prevents cardiovascular remodelling in spontaneously hypertensive rat by modulation of energy metabolism

• Published in: Clinical and experimental pharmacology & physiology Vol. 49; no. 1; pp. 35 - 45
• Main Authors: Potnuri, Ajay Godwin, Purushothaman, Sreeja, Saheera, Sherin, Nair, Renuka R.
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.01.2022
• Subjects: Animals; Anomalies; Antioxidants; Antioxidants - pharmacology; Blood Pressure - drug effects; cardiac hypertrophy; cardiac metabolism; Cardiovascular diseases; Cardiovascular system; Cyclic N-Oxides - pharmacology; Echocardiography; Energy metabolism; Energy Metabolism - drug effects; Fatty acids; Fibrosis; Health risks; Heart; Heart Rate - drug effects; Hypertension; Hypertension - drug therapy; Hypertrophy; LC–MS; Lysates; Male; Metabolism; Mitochondria; mitochondria targeted antioxidant; Mitochondria, Heart - drug effects; Oxidants; Oxidation; Oxidative stress; Oxidizing agents; proteomic analysis; Rats; Rats, Inbred SHR; Rats, Wistar; Reactive oxygen species; Spin Labels; spontaneously hypertensive rat; Structure-function relationships; Tempol; Ventricle; Ventricular Remodeling - drug effects; spontaneously hypertensive rat; LC-MS; cardiac hypertrophy; mitochondria targeted antioxidant; cardiac metabolism; proteomic analysis
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13585

Hypertension induced left ventricular hypertrophy (LVH) augments the risk of cardiovascular anomalies. Mitochondrial alterations result in oxidative stress, accompanied by decrease in fatty acid oxidation, leading to the activation of the hypertrophic program. Targeted antioxidants are expected to reduce mitochondrial reactive oxygen species more effectively than general antioxidants. This study was designed to assess whether the mito‐targeted antioxidant, Mito‐Tempol (Mito‐TEMP) is more effective than the general oxidant, Tempol (TEMP) in reduction of hypertension and hypertrophy and prevention of shift in cardiac energy metabolism. Spontaneously hypertensive rats were administered either TEMP (20 mg/kg/day) or Mito‐TEMP (2 mg/kg/day) intraperitoneally for 30 days. Post treatment, animals were subjected to 2D‐echocardiography. Myocardial lysates were subjected to RPLC – LTQ‐Orbitrap‐MS analysis. Mid‐ventricular sections were probed for markers of energy metabolism and fibrosis. The beneficial effect on cardiovascular structure and function was significantly higher for Mito‐TEMP. Increase in mitochondrial antioxidants and stimulation of fatty acid metabolism; with significant improvement in cardiovascular function was apparent in spontaneously hypertensive rats (SHR) treated with Mito‐TEMP. The study indicates that Mito‐TEMP is superior to its non‐ targeted isoform in preventing hypertension induced LVH, and the beneficial effects on heart are possibly mediated by reversal of metabolic remodelling.