title: Aliskiren, exendin-4, and insulin: their impact on endothelin receptor subtype(s) regulation/binding in type 1 diabetic rat hearts.
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 [(125)I]-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.
authors.affiliation: a Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon.
authors.forename: Sawsan M
authors.initials: SM
authors.lastname: Al Lafi
authors.forename: Shushan B
authors.initials: SB
authors.lastname: Artinian
authors.forename: Suzan S
authors.initials: SS
authors.lastname: Boutary
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Zwainy
authors.forename: Khalil M
authors.initials: KM
authors.lastname: Bitar
authors.forename: Anwar B
authors.initials: AB
authors.lastname: Bikhazi
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D000077270:Exenatide; D005650:Fumarates / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*
chemical_list: D000577:Amides; D019332:Endothelin-1; D005650:Fumarates; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014688:Venoms; C446481:aliskiren; D013311:Streptozocin; D000077270:Exenatide