title: Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats.
abstract: Many clinical trials have demonstrated that angiotensin converting enzyme inhibitors have protective effects on organ damage, suggesting the importance of inhibition of the renin-angiotensin system. In this study, we investigated the effects of a non-depressor dose of imidapril on organ damage induced by diabetes and hypertension. Diabetes was induced by an intravenous injection of streptozotocin (STZ, 40 mg/kg) in 15-week-old male spontaneously hypertensive rats (SHR). Imidapril (2 mg/kg/day) or vehicle was given orally for 28 days, and then the heart weight, left ventricle mass (LVM), urinary albumin excretion (UAE) and endothelial function were examined, as well as the urinary NOx level and local hepatocyte growth factor (HGF) expression. There were no significant differences between the treated groups in systolic blood pressure and plasma parameters. On the other hand, UAE was significantly suppressed in the imidapril-treated group (450+/-44 mg/day) compared to the vehicle-treated group (963+/-182 mg/day) (p<0.01). Moreover, endothelial function assessed by dilative reaction to acetylcholine as well as cardiac hypertrophy assessed by both heart/body weight ratio and LVM were significantly improved in the imidapril-treated group (p<0.05 and p<0.01, respectively). The urinary NOx concentration and local HGF expression in vessel walls were also significantly increased in the imidapril-treated group (p<0.01). A non-depressor dose of imidapril showed protective effects against organ damage in diabetic SHR, which may be partially due to the increase of HGF and NO.
authors.affiliation: Division of Clinical Gene Therapy, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan. tomita@med.kawasaki-m.ac.jp
authors.forename: Naruya
authors.initials: N
authors.lastname: Tomita
authors.forename: Keita
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Izawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kunugiza
authors.forename: Mariana K
authors.initials: MK
authors.lastname: Osako
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000737:chemistry; D006352:Heart Ventricles / Q000033:anatomy & histology; D017228:Hepatocyte Growth Factor / Q000032:analysis; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D048289:Imidazolidines / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D048289:Imidazolidines; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; C065166:imidapril