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- Title
Endopeptidase inhibition attenuates the contraction induced by big endothelin-1 of isolated human penile erectile tissue.
- Authors
Shahin, P.; Rahardjo, H. E.; Bannowsky, A.; Tsikas, D.; Sohn, M.; Kuczyk, M. A.; Ückert, S.
- Abstract
Peptides, such as C- type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 μm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 μm), CNP and VIP (0.1 nm - 1 μm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre- exposure to 10 μm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.
- Subjects
IMPOTENCE; NORADRENALINE; ENDOPEPTIDASES; MUSCLE contraction; NATRIURETIC peptides; ENDOTHELIUM diseases
- Publication
Andrologia, 2018, Vol 50, Issue 5, p1
- ISSN
0303-4569
- Publication type
Article
- DOI
10.1111/and.13008