Induction of tissue angiotensinⅡ-forming activity in two-kidney,one-clip hypertensive hamster model

• 作者: Eiji Yahiro Hidenori Urata Kanta Fujimi Keijiro Saku Sankar Devarajan Satomi Abe Yoshinari Uehara
• 来源期刊: 世界高血压杂志
• 学科: 医学
• 关键词: CHYMASE local RENIN ANGIOTENSIN system angiotensinⅡ TISSUE remodeling hypertension
• 年，卷（期）: 2013,（2）
• 页码范围: 9-17
• 页数: 9页
• 分类号: R972

摘要

AIM:To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS:A two-kidney,one-clip(2K1C)hypertension model was developed in Syrian hamsters,which have a human-type chymase.Either an angiotensin(Ang)converting enzyme(ACE)inhibitor(ACE-I;temocapril,30 mg/kg per day),AngⅡtype 1 receptor antagonist(ARB;CS866,10 mg/kg per day),or vehicle was administered,beginning 2 wk after renal artery clipping and continued for 16 wk.At the end of this protocol,hearts,aortas,and lungs were removed,and total AngⅡ-forming activities and ACE-and chymasedependent AngⅡ-forming activities were determined.RESULTS:After renal artery clipping,systolic blood pressure in the vehicle group was significantly higher compared with that in a sham-operated group throughout the experimental period.Both ACE-I and ARB treatments revealed similar antihypertensive effects.Moreover,in the vehicle group,cardiac total and chymase-dependent AngⅡ-forming activities significantly increased at 18 wk after clipping.Further,cardiac total and chymase-dependent AngⅡ-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk.In addition,chymase-dependent AngⅡ-forming activity significantly increased in the aorta,although these changes were inhibited only by ARB.ARB treatment was more effective compared with ACE-I treatment in reversing the changes in tissue AngⅡformation,particularly in the aorta,despite their similar antihypertensive effects.CONCLUSION:Chymase does not play a major role in maintaining blood pressure and tissue ACE and chymase are regulated in a tissue-dependent manner in 2K1C hamster.