title: The calcium channel antagonist benidipine reduces plasma and cardiac endothelin-1 levels in type II diabetic rat model.
abstract: Cardiovascular complications are the central feature of type 2 diabetes mellitus, and insulin resistance is an early clinical manifestation of type 2 diabetes mellitus. Calcium channel blockers are widely used to treat cardiovascular diseases in diabetic patients; however, it remains unknown how endothelin-1 (ET-1) is altered and associated with cardiac lesions at the insulin-resistant early stage of type 2 diabetes mellitus, and, if so, whether calcium channel blockers can reverse such alterations. We examined plasma and cardiac expression of ET-1 in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous model of human type 2 diabetes mellitus. At 8 weeks of age, OLETF rats were treated for 12 weeks with a long acting calcium channel blocker, benidipine (3 mg/kg per day p.o.) (BEN, n = 15), or with vehicle (OLETF, n = 15), and age-matched genetic control, male Long-Evans Tokushima Otsuka (LETO) rats were also used (n = 15). Blood pressure was significantly higher in OLETF than LETO rats, and benidipine treatment of OLETF rats for 12 weeks did not reduce their blood pressure significantly. Plasma and cardiac levels of ET-1 were significantly higher in OLETF compared with LETO rats (both P < 0.01), and were reversed after benidipine treatment. Our results suggest that ET-1 plays a pivotal role in the pathogenesis of cardiac complications at the insulin-resistant stage of diabetes mellitus, and that benidipine treatment may have a beneficial effect on these complications.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D000367:Age Factors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; C061004:benidipine