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Research ArticleCARDIOVASCULAR

Multiple Pathways of Angiotensin I Conversion and Their Functional Role in the Canine Penile Corpus Cavernosum

Yusaku Iwamoto, Keifu Song, Shinji Takai, Mayumi Yamada, Denan Jin, Masato Sakaguchi, Haruhiko Ueda, Yoji Katsuoka and Mizuo Miyazaki
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 43-48;
Yusaku Iwamoto
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Keifu Song
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Shinji Takai
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Mayumi Yamada
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Denan Jin
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Masato Sakaguchi
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Haruhiko Ueda
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Yoji Katsuoka
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Mizuo Miyazaki
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Abstract

Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 ± 1.7 mU/mg of protein, mean ± S.E.M., n = 8) and chymase-like enzyme (4.0 ± 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 × 10−7 M) induced a tension of 0.17 ± 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10−6 M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10−4 M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and125I-[Sar1,Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10−6 M), markedly displaced 125I-[Sar1,Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.

Footnotes

  • Abbreviations:
    RAS
    renin angiotensin system
    Ang
    angiotensin
    ACE
    angiotensin-converting enzyme
    BSA
    bovine serum albumin
    • Received December 28, 2000.
    • Accepted April 4, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleCARDIOVASCULAR

Multiple Pathways of Angiotensin I Conversion and Their Functional Role in the Canine Penile Corpus Cavernosum

Yusaku Iwamoto, Keifu Song, Shinji Takai, Mayumi Yamada, Denan Jin, Masato Sakaguchi, Haruhiko Ueda, Yoji Katsuoka and Mizuo Miyazaki
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 43-48;

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Research ArticleCARDIOVASCULAR

Multiple Pathways of Angiotensin I Conversion and Their Functional Role in the Canine Penile Corpus Cavernosum

Yusaku Iwamoto, Keifu Song, Shinji Takai, Mayumi Yamada, Denan Jin, Masato Sakaguchi, Haruhiko Ueda, Yoji Katsuoka and Mizuo Miyazaki
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 43-48;
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