title: Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.
abstract: Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation.
authors.affiliation: Faculty of Pharmacy, Department of Pharmacology, Istanbul University, 34116 Beyazıt, Istanbul, Turkey. gokce_topal@hotmail.com
authors.forename: Gökçe
authors.initials: G
authors.lastname: Topal
authors.forename: Ebru
authors.initials: E
authors.lastname: Koç
authors.forename: Cetin
authors.initials: C
authors.lastname: Karaca
authors.forename: Tuncay
authors.initials: T
authors.lastname: Altuğ
authors.forename: Bülent
authors.initials: B
authors.lastname: Ergin
authors.forename: Cihan
authors.initials: C
authors.lastname: Demirci
authors.forename: Gülay
authors.initials: G
authors.lastname: Melikoğlu
authors.forename: Ali H
authors.initials: AH
authors.lastname: Meriçli
authors.forename: Mine
authors.initials: M
authors.lastname: Kucur
authors.forename: Osman
authors.initials: O
authors.lastname: Ozdemir
authors.forename: B Sönmez
authors.initials: BS
authors.lastname: Uydeş Doğan
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D027825:Crataegus; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D008315:Malondialdehyde; C007145:crataegus extract; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat