title: Melatonin restores endothelium-dependent relaxation in aortic rings of pancreatectomized rats.
abstract: In rats turned hyperglycemic by a subtotal pancreatectomy, a decreased relaxation response of aortic rings to acetylcholine (ACh) was found; this effect was amplified by preincubation in a high glucose medium (44 mmol/L). The relaxation response to ACh did not occur in endothelium-denuded rings or after the aortic rings were exposed to l-nitro-arginine methyl ester [L-NAME, a nitric oxide (NO) synthase inhibitor]. Incubation with the NO donor sodium nitroprusside (SNP) restored the impaired relaxation response seen in endothelium-denuded or L-NAME-treated aortic rings. Pancreatectomy decreased the vasorelaxation of aortic rings caused by SNP. Only in pancreatectomized rats, incubation in a high glucose medium impaired the relaxation effect of SNP. To assess whether melatonin preincubation reversed the impaired relaxation response to ACh (intact endothelium aortic rings) or to SNP (endothelium-denuded or L-NAME-treated rings) in hyperglycemic rats, cumulative dose-response curves were performed in the presence of 10(-5) mol/L melatonin. Melatonin preincubation did not modify ACh-induced relaxation of aortic rings in a normal glucose concentration but was highly effective in preventing the impairment of relaxation caused by a high glucose solution. Melatonin was also effective in restoring the impaired SNP-induced vasorelaxation seen in endothelium-denuded or L-NAME-treated aortic rings from hyperglycemic rats. The results further support the improvement by melatonin of the endothelial-mediated relaxation in blood vessels of diabetic rats.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Reyes-Toso
authors.forename: Laura M
authors.initials: LM
authors.lastname: Linares
authors.forename: Conrado R
authors.initials: CR
authors.lastname: Ricci
authors.forename: Daniel
authors.initials: D
authors.lastname: Obaya-Naredo
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Pinto
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Rodríguez
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cardinali
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010180:Pancreatectomy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009599:Nitroprusside; D005947:Glucose; D008550:Melatonin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester