title: Cyclohexenonic long-chain fatty alcohol has therapeutic effects on diabetes-induced angiopathy in the rat aorta.
abstract: We studied the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
authors.affiliation: Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University Faculty of Medicine, 86 Nishimachi, Yonago, 683-8503, Japan.
authors.forename: Chiko
authors.initials: C
authors.lastname: Shinbori
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Itaru
authors.initials: I
authors.lastname: Satoh
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Kono
authors.forename: Takuya
authors.initials: T
authors.lastname: Hanada
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Kaori
authors.initials: K
authors.lastname: Adachi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Satoh
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005233:Fatty Alcohols / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D005233:Fatty Alcohols; D012333:RNA, Messenger; D043587:Receptor, Muscarinic M3; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C051942:1-hexacosanol