Abstract 14050: Soluble Epoxide Hydrolase Inhibitor t-TUCB Protects Heart From Ischemia/reperfusion-induced Myocardial Damage and Endothelial Dysfunction in Hypertension and Diabetes.
Introduction: Damage to myocardium of heart may leads to congestive heart failure. Earlier, we reported that soluble epoxide hydrolase inhibitors (sEHi) can protect heart against isoproterenol-induced myocardial infarction.
Hypothesis: We hypothesized that sEHi t-TUCB might protect heart from ischemia/reperfusion (I/R)-induced injury and endothelial dysfunction in hypertension and diabetes.
Methods: Hearts were isolated from rat and mounted in modified Langendorff’s apparatus. Hearts were rendered ischemic by stopping flow of Krebs-Henseleit (K-H) solution for 15 min and reperfusion of K-H solution for 30 min was used to induce myocardial injury. Effect of I/R was evaluated on heart rate, resting tension (RT) and myocardial damage which was quantified by evaluating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activities in heart perfusate along with TTC staining of heart. Further, effect of I/R injury on fructose-induced hypertension and streptozotocin-induced diabetes was evaluated. Pretreatment of t-TUCB (0.1 and 0.3 mg/kg/day, p.o., 28 days) on myocardial injury was evaluated along with its influence on relaxant effect of acetylcholine on aortas from hypertensive and diabetic rats ex vivo as a marker of endothelial function.
Results: I/R decreased heart rate but increased the RT significantly (p < 0.05) in normal, hypertensive and diabetic rats. Treatment of t-TUCB significantly minimized decrease in heart rate and the increase in RT. I/R also significantly increased the myocardial damage as evident from the increase in activity of LDH and CK-MB in perfusate and TTC staining. Hypertension and diabetes aggravated I/R-induced injury. The treatment of t-TUCB to normal, hypertensive and diabetic rats significantly decreased (p < 0.05) the activity of LDH and CK-MB and myocardial damage. Endothelial function was reduced significantly (p < 0.05) in aorta of hypertensive and diabetic rats in comparison to normal rats as evident from the decrease in relaxant effect of Ach on phenylephrine pre-contracted blood vessel. Treatment of t-TUCB ameliorated the endothelial dysfunction observed in hypertensive and diabetic rats.
Conclusions: The sEHi t-TUCB can protect heart from I/R-induced damage and prevent endothelial dysfunction.
Author Disclosures: S.K. Goswami: None. O. Islam: None. P. Patil: None. R. Razdan: None. M.N. Inamdar: None. R. Mohammed: None. J. Mathew: None. S.H. Hwang: None. B. Inceoglu: None. B.D. Hammock: None.
- © 2016 by American Heart Association, Inc.