title: Effects of glucagon-like peptide-1 in diabetic rat small resistance arteries.
abstract: We investigated the functional effects of glucagon-like peptide-1 [GLP-1(7-36)] and GLP-1(9-36) and the mechanism(s) playing a role in the effects of these agents in isolated small resistance arteries from control and diabetic rats. Cumulative concentrations of GLP-1(7-36) and GLP-1(9-36) produced concentration-dependent relaxations in endothelium-intact but not endothelium-denuded arteries that were significantly decreased in diabetic rats. GLP-1 receptor antagonist exendin(9-39) significantly inhibited responses to GLP-1 analogs. Nitric oxide/cyclic guanosine monophosphate pathway blockers, but not indomethacin, significantly decreased responses to GLP-1(7-36) or GLP-1(9-36) in control and diabetic rats. 4-Aminopyridine or glibenclamide incubation did not alter relaxations to GLP-1 analogs. GLP-1(7-36)- and GLP-1(9-36)-induced relaxations were blunted significantly and to similar extends by charybdotoxin and apamin combination in control and diabetic rats. Catalase did not affect, whereas superoxide dismutase (SOD) caused a significant increase in relaxations to GLP-1 analogs only in diabetic rats. We provided evidence about the relaxant effects of GLP-1(7-36) and GLP-1(9-36) in resistance arteries that were reduced in diabetic rats. Both calcium-activated potassium channels and endothelium played a major role in relaxations. Increment in certain reactive oxygen species and/or reduction in superoxide dismutase function might play a role in reduced relaxant responses of resistance arteries to GLP-1(7-36) and GLP-1(9-36) in diabetic rats.
authors.affiliation: Department of Medical Pharmacology, Medical Faculty, Akdeniz University, Antalya, Turkey.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Bayram
authors.forename: Cahit
authors.initials: C
authors.lastname: Nacitarhan
authors.forename: Sadi S
authors.initials: SS
authors.lastname: Ozdem
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D017382:Reactive Oxygen Species; C114437:glucagon-like peptide-1 (9-36)-amide; C061970:glucagon-like peptide 1 (7-36); D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D015761:4-Aminopyridine; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D005905:Glyburide