[Frontiers in Bioscience E2, 972-979, June 1, 2010]

Add-on blockade of (pro)renin receptor in imidapril-treated diabetic SHRsp

Yasufumi Seki1, Atsuhiro Ichihara2, Yuki Mizuguchi1, Mariyo Sakoda1, Asako Kurauchi-Mito1, Tatsuya Narita1, Kenichiro Kinouchi1, Kanako Bokuda1, Hiroshi Itoh1

1Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Department of Endocrinology and Anti-Aging Medicine, Keio University School of Medicine, Tokyo, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Method
3.1. Animals
3.2. Experimental protocols
3.3. Morphological evaluation
3.4. Measurements of angiotensin peptides
3.5. Real-time Quantitative RT-PCR Analysis
3.6. Statistical Analyses
4. Results
4.1. Body weight, blood glucose, and mean arterial pressure
4.2. Glomerular activated prorenin, proteinuria and renal morphology
4.3. Tissue angiotensin II content and TGFβ mRNA expression in the kidneys
4.4. Heart weight and cardiac fibrosis
4.5. Tissue angiotensin II content and collagen I mRNA expression in the heart
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

To examine the involvement of (pro)renin receptor in the accelerated organ damage in streptozotocin-induced diabetic male SHRsp, the rats fed a high-salt diet were divided into 5 groups: a group treated with the vehicle, a group treated with 15 mg/kg/day of imidapril (ACEi), a group treated with 60 mg/kg/day of imidapril (High ACEi), a group treated with handle region peptide (HRP), and a group treated with both ACEi and HRP (ACEi+HRP). After 8 weeks, the arterial pressure was similar in the vehicle and HRP groups and decreased in the ACEi-treated groups. The renal angiotensin II content decreased similarly in the groups treated with ACEi and/or HRP. Urinary protein excretion also decreased in the ACEi, High ACEi, and HRP groups and significantly further decreased in the ACEi+HRP group. The heart weight of the ACEi+HRP group was significantly lower than that of any other groups, although the cardiac angiotensin II levels decreased similarly in the groups treated with ACEi and/or HRP. Thus, (pro)renin receptor contributes to the accelerated pathogenesis in the heart and kidneys of diabetic SHRsp.