Wagner J, Drab M, Bohlender J, Amann K, Wienen W, Ganten D
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Clin Exp Hypertens. 1998 Feb;20(2):205-21. doi: 10.3109/10641969809053215.
The aim of the study was to assess the effects of chronic angiotensin I receptor blockade on blood pressure, the renin-angiotensin system in plasma and kidney and the extent of renal damage in spontaneously hypertensive rats of the stroke prone strain (SHRsp). Four months old male SHRsp rats were orally treated with a high (10 mg/kg b.w. per day) or a low dose (1 mg/kg b.w. per day) of the AT1 receptor antagonist Telmisartan and compared to Losartan- (20 mg/kg b.w. per day), Captopril-treated (50 mg/kg b.w. per day) or untreated control groups for 38 days. Despite a similar extent of blood pressure reduction in all groups (except low dose Telmisartan), high dose Telmisartan but not Losartan or Captopril significantly reduced left ventricular weight by 24% compared to controls (p<0.05). Renal damage as assessed by urinary albumin or glomerulosclerosis index was significantly reduced in all treatment groups (p<0.02). Plasma renin concentration was significantly elevated (p<0.02) and plasma angiotensinogen significantly lowered (p<0.05) in all pharmacologically treated group compared to controls. In the kidney, renin-mRNA as well as AT1 receptor gene expression were elevated in all treatment groups, but no significant changes were found for renal angiotensinogen-mRNA. Chronic oral treatment of genetically hypertensive rats by the AT1 receptor antagonist Telmisartan reveals a blood pressure lowering and reno-protective effect of this drug comparable to other AT1 receptor antagonists or converting enzyme inhibitors, and demonstrates a marked reduction of cardiac hypertrophy by Telmisartan in this model.
本研究的目的是评估慢性血管紧张素I受体阻断对血压、血浆和肾脏中的肾素-血管紧张素系统以及易中风品系自发性高血压大鼠（SHRsp）肾损伤程度的影响。4月龄雄性SHRsp大鼠分别口服高剂量（每天10mg/kg体重）或低剂量（每天1mg/kg体重）的AT1受体拮抗剂替米沙坦，并与氯沙坦治疗组（每天20mg/kg体重）、卡托普利治疗组（每天50mg/kg体重）或未治疗的对照组进行比较，为期38天。尽管所有组（低剂量替米沙坦组除外）的血压降低程度相似，但与对照组相比，高剂量替米沙坦显著降低左心室重量24%（p<0.05），而氯沙坦或卡托普利则无此作用。通过尿白蛋白或肾小球硬化指数评估的肾损伤在所有治疗组中均显著降低（p<0.02）。与对照组相比，所有药物治疗组的血浆肾素浓度显著升高（p<0.02），血浆血管紧张素原显著降低（p<0.05）。在肾脏中，所有治疗组的肾素mRNA以及AT1受体基因表达均升高，但肾血管紧张素原mRNA未发现显著变化。AT1受体拮抗剂替米沙坦对遗传性高血压大鼠进行慢性口服治疗，显示该药物具有与其他AT1受体拮抗剂或转化酶抑制剂相当的降压和肾保护作用，并在该模型中证明替米沙坦可显著减轻心脏肥大。
