Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats.
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.
Tomita
Naruya
N
Division of Clinical Gene Therapy, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan. tomita@med.kawasaki-m.ac.jp
Yamasaki
Keita
K
Izawa
Keiko
K
Kunugiza
Yasuo
Y
Osako
Mariana K
MK
Ogihara
Toshio
T
Morishita
Ryuichi
R
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D048289:Imidazolidines; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; C065166:imidapril