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Cardiac Remodeling and Failure pp 279–292Cite as

The Effect of Bradykinin on the Remodeling of Pressure-Overloaded Myocardium

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 5))

Abstract

ACE inhibitors prevent not only hypertension but also cardiac hypertrophy and fibrosis. These mechanisms are accompanied by both the inhibition of angiotensin II formation and the catabolism of bradykinin (BK). Increased BK level stimulates expression of nitric oxide (NO) synthase (NOS) and induces prostaglandins, both of which are powerful vasodilator factors. The direct effect of BK against cardiac hypertrophy had not been elucidated. This study was performed to examine cardioprotective effects of BK in hypertrophic models. Renovascular hypertension (RHT) rats were treated with BK (1000ng/kg/day), BK + HOE140 (BK B2 antagonist) and BK + L-NAME (NOS inhibitor) for four weeks. Blood pressure was measured and echocadiographic analysis was performed during treatment. Histological analysis was done to confirm the anti-hypertrophic effect of BK.

BK slightly reduced systolic blood pressure from 220 ± 8 mmHg to 190 ± 8 mmHg in RHT rats. This change was blocked by HOE 140 or L-NAME. M-mode of echocardiography revealed significant improvement of cardiac remodeling with BK treatment. However, co-treatment with HOE 140 or L-NAME reversed the anti-hypertrophic action of BK. Heart weight to body weight ratios were as follows: control, 2.9 ±0.1; RHT, 4.7 ± 0.2; BK, 3.9 ± 0.1; BK + HOE140, 4.6 ± 0.8; BK + L-NAME, 4.7 ± 0.1. Cardiac fibrosis and collagen accumulation in particular were inhibited by treatment with BK, but HOE 140 and L-NAME counteracted these changes.

These results indicate that bradykinin directly inhibits the progression of cardiac hypertrophy or cardiac fibrosis due to the increase in NO release via the BK B2 receptor. The bradykinin-NO pathway may play an important role in the progression of cardiac remodeling.

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Japan

    Seibu Mochizuki, Makoto Nagai, Taro Date, Hideki Sasaki, Satoshi Takeda, Kazuaki Horikoshi, Takehiko Izumi, Shingo Seki & Masayuki Taniguchi

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  1. Seibu Mochizuki
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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Pawan K. Singal PhD, DSc (Professor), Ian M. C. Dixon PhD (Associate Professor), Lorrie A. Kirshenbaum PhD (Associate Professor) & Naranjan S. Dhalla PhD, MD (HON), DSc (HON) (Distinguished Professor and Director) (Professor),  (Associate Professor),  (Associate Professor) &  (Distinguished Professor and Director)

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Mochizuki, S. et al. (2003). The Effect of Bradykinin on the Remodeling of Pressure-Overloaded Myocardium. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_19

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  • DOI: https://doi.org/10.1007/978-1-4419-9262-8_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4864-1

  • Online ISBN: 978-1-4419-9262-8

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