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Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue
Author(s) -
Shahin P.,
Rahardjo H. E.,
Bannowsky A.,
Tsikas D.,
Sohn M.,
Kuczyk M. A.,
Ückert S.
Publication year - 2018
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.13008
Subject(s) - vasoactive intestinal peptide , neprilysin , contraction (grammar) , endocrinology , medicine , erectile dysfunction , endothelin receptor , smooth muscle , endothelin 1 , chemistry , natriuretic peptide , erectile tissue , endopeptidase , neuropeptide , enzyme , biochemistry , receptor , heart failure
Summary 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 μ m ), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 n m – 10 μ m ), CNP and VIP (0.1 n m – 1 μ m ), were investigated. Effects of CNP , VIP and Big ET ‐1 (0.1 n m – 100 n m ) on the tissue tension were also evaluated following pre‐exposure to 10 μ m 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.