title: The beneficial in vitro effects of lovastatin and chelerythrine on relaxatory response to acetylcholine in the perfused mesentric bed isolated from diabetic rats.
abstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease. Endothelial dysfunction (i.e. decreased endothelium-dependent vasorelaxation) plays a key role in the pathogenesis of diabetic vascular disease. The present study was undertaken to determine whether diabetes induced by streptozotocin alters mesenteric responses to vasodilators and, if so, to study the acute in vitro effects of lovastatin and chelerythrine. Endothelial function was assessed in constantly perfused preparation removed from rats, 12 weeks after treatment with either saline or streptozotocin (45 mg/kg, intraperitoneally). In pre-contracted mesenteric beds (with 100 microM phenylephrine) removed from diabetic rats, the concentration response curve to acetylcholine, but not to sodium nitroprusside, was significantly reduced. Perfusion with lovastatin (10 microM for 20 min) or chelerythrine (1 microM for 20 min) significantly improved the acetylcholine-mediated relaxation in preparations removed from diabetic but not control rats. Pre-incubation of tissue with N(G)-nitro-L-argenine methyl ester hydrochloride (10 microM for 20 min) inhibited the beneficial effect of lovastatin but not chelerythrine. Pre-treatment of tissue with indomethacin (10 microM for 20 min) did not modify the effects of lovastatin or chelerythrine on acetylcholine responses. The present results demonstrate that endothelial dysfunction induced by diabetes (in a resistant vasculature, such as rat mesenteric bed) may be improved by an acute exposure to either lovastatin or chelerythrine. Furthermore, our results suggest that the beneficial effect of lovastatin is mediated via the nitric oxide pathway.
authors.affiliation: Department of Physiology & Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. z_fatehi@yahoo.com
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fatehi-Hassanabad
authors.forename: Mohsen
authors.initials: M
authors.lastname: Imen-Shahidi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fatehi
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Farrokhfall
authors.forename: Heidar
authors.initials: H
authors.lastname: Parsaeei
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D010617:Phenanthridines / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010617:Phenanthridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D008148:Lovastatin; C016299:chelerythrine; D011493:Protein Kinase C; D000109:Acetylcholine