RT Journal Article
SR Electronic
T1 Multiple Pathways of Angiotensin I Conversion and Their Functional Role in the Canine Penile Corpus Cavernosum
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 43
OP 48
VO 298
IS 1
A1 Yusaku Iwamoto
A1 Keifu Song
A1 Shinji Takai
A1 Mayumi Yamada
A1 Denan Jin
A1 Masato Sakaguchi
A1 Haruhiko Ueda
A1 Yoji Katsuoka
A1 Mizuo Miyazaki
YR 2001
UL http://jpet.aspetjournals.org/content/298/1/43.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics