title: Na+/Ca2+ exchanger inhibitor restores endothelium-dependent relaxation in diabetic rat aorta.
abstract: The aims of this study were to examine the effects of KB-R7943, an inhibitor of Na(+)/Ca(2+) exchanger, on the endothelium-dependent relaxation (EDR) in diabetic rat aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured in aortic rings of nondiabetic and streptozotocin-diabetic rats. Diabetes mellitus was induced by single injection of streptozotocin (60 mg/kg). The treated rats received 0.01 or 0.1 mg/kg/day of KB-R7943 for 8 weeks. ACh-induced relaxation was impaired in diabetic compared to control rings and the vasodilatation to SNP was unaffected. Treatment with KB-R7943 markedly enhanced relaxation to ACh in diabetic but not in control rings. KB-R7943 significantly increased superoxide dismutase (SOD) activity and the nitric oxide (NO) release. These results suggest that KB-R7943 can restore impaired EDR in aortic rings of diabetic rats, which may be related to scavenging oxygen free radicals and enhancing NO production.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: X-F
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: T-T
authors.initials: TT
authors.lastname: Wan
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Su
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000378:metabolism; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D019831:Sodium-Calcium Exchanger; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D013890:Thiourea; D000109:Acetylcholine