Effect of Omega‐3 PUFA on Endothelin‐1 Receptors in Normal and Type 1 Diabetic Rat Hearts

Abstract

Cardiovascular disease is a major complication in diabetes. Its management includes renin‐angiotensin‐system components, endothelial factors (Nitric Oxide), or Endothelin‐1 (ET‐1) regulation. This study focuses on long‐term ET‐1 receptor regulation by ω‐3 and Statin at coronary endothelium (CE) and cardiomyocytes (CM) levels in diabetic rats. Sprague Dawley male rats (n=24) were assigned to 7 groups: normal (N); streptozotocin (STZ)‐induced diabetic (D); normal rats treated with ω‐3 (0.085g/kg) (NO) or Statin (0.89 mg/kg) (NS); diabetic rats treated with ω‐3(DO), Statin (DS) or both (DOS). After a month of treatment, their hearts were perfused with [125I]‐ET‐1 (CHAPS‐untreated for CE and CHAPS‐treated for CM analyses) to estimate ET‐1 receptor‐binding affinity (τ = 1/K−n) on CE and CM. Tissue samples were analyzed by western blot for ET‐1 receptor subtypes A (ETAR) and B (ETBR). Residency time constant, τ, of ETBR increased in all groups as compared to N (1.05 ± 0.06), except for DS (1.18 ± 0.07) which was normalized. As for ETAR, τ increased in all groups but normalized in DO (1.18 ± 0.07). In western blot, ETAR increased (1.31 ± 0.09 vs 0.96 ± 0.05) and ETBR decreased (1.00 ± 0.06 vs 1.30 ± 0.07) in D, but both values were corrected in all other groups. Thus, ω‐3 and Statin therapy improved ETAR and ETBR functions respectively in diabetics; however, ω‐3 dosage regimens needs further analysis in healthy subjects.