Original Article
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World J Hypertens. May 23, 2013; 3(2): 9-17
Published online May 23, 2013. doi: 10.5494/wjh.v3.i2.9
Induction of tissue angiotensin II-forming activity in two-kidney, one-clip hypertensive hamster model
Yoshinari Uehara, Kanta Fujimi, Eiji Yahiro, Satomi Abe, Sankar Devarajan, Keijiro Saku, Hidenori Urata
Yoshinari Uehara, Kanta Fujimi, Eiji Yahiro, Satomi Abe, Keijiro Saku, Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan
Sankar Devarajan, Hidenori Urata, Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Chikushino 818-8502, Japan
Author contributions: All authors contributed to this work. Uehara Y, Fujimi K and Yahiro E contributed equally to this work.
Correspondence to: Yoshinari Uehara, MD, PhD, Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. ueharay@fukuoka-u.ac.jp
Telephone: +81-92-8011011 Fax: +81-92-8652692
Received: April 19, 2013
Revised: May 9, 2013
Accepted: May 20, 2013
Published online: May 23, 2013
Abstract

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), Ang II type 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 Ang II-forming activities and ACE- and chymase-dependent Ang II-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 Ang II-forming activities significantly increased at 18 wk after clipping. Further, cardiac total and chymase-dependent Ang II-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk. In addition, chymase-dependent Ang II-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 Ang II formation, 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.

Keywords: Chymase, Local renin angiotensin system, Angiotensin II, Tissue remodeling, Hypertension

Core tip: There are several pathways that can produce angiotensin (Ang) II in human tissues, which are involved in remodeling of the cardiovascular system. Among these, chymase has been exhibited the greatest Ang II-forming enzyme in human heart. In hypertensive hamster, blood pressure was significantly elevated, and both Ang converting enzyme (ACE) inhibitor (ACE-I) and Ang II type 1 receptor antagonist (ARB) revealed similar antihypertensive effects. Interestingly, cardiac chymase-dependent Ang II-formation decreased after ACE-I or ARB treatment. In addition, chymase-dependent Ang II-formation increased in the aorta, although these changes were inhibited only by ARB. ACE and chymase were regulated in a tissue-dependent manner in hypertensive hamsters, and the both enzymes were independently regulated.