Aliskiren, exendin-4, and insulin: their impact on endothelin receptor subtype(s) regulation/binding in type 1 diabetic rat hearts

Author:

Al Lafi Sawsan M.1,Artinian Shushan B.1,Boutary Suzan S.1,Zwainy Nadine S.1,Bitar Khalil M.2,Bikhazi Anwar B.1

Affiliation:

1. Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon.

2. Department of Physics, Faculty of Arts and Sciences, American University of Beirut, Beirut 11-0236, Lebanon.

Abstract

This study focuses on the impact of aliskiren and (or) glucagon-like peptide-1 analogue on the binding affinity/regulation of endothelin-1 (ET-1) to its receptor subtypes A (ETAR) and B (ETBR) at the level of the coronary endothelium and the cardiomyocytes in a type-1 diabetic rat model. Seven groups were used: (i) normal rats, (ii) rats with induced diabetes, (iii) rats with induced diabetes that were treated with insulin, (iv) rats with induced diabetes that were treated with exendin-4, (v) rats with induced diabetes that were treated with aliskiren, (vi) rats with induced diabetes that were co-treated with insulin plus aliskiren, and (vii) rats with induced diabetes that were co-treated with exendin-4 plus aliskiren. Heart perfusion with [125I]-ET-1 was employed to estimate ET-1 binding affinity (τ = 1/K–n) to ETAR and ETBR at the level of the coronary endothelium and the cardiomyocytes. Plasma ET-1 levels were measured using enzyme immunoassay, whereas densities of ETAR and ETBR were detected using Western blot. No significance differences were detected in the τ of ETAR and ETBR between normal and diabetic in cardiomyocytes and the coronary endothelium. Exendin-4 normalized the τ value for ETAR and ETBR on coronary endothelium, while aliskiren normalized it on cardiomyocytes. Furthermore, ETAR and ETBR densities were normalized with monotreatments of aliskiren and exendin-4, compared with up-regulated ETAR and down-regulated ETBR band densities in the diabetic animals. Our data indicate that aliskiren alleviates diabetes-associated hypertrophy in type 1 diabetes mellitus.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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