Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5830655 | European Journal of Pharmacology | 2008 | 7 Pages |
Abstract
We investigated the contractile response of the lower urinary tract to endothelin-1 in vitro (rabbits) and in vivo (dogs). We also assessed the effects of a selective endothelin ETA receptor antagonist, (E)-N-[6-methoxy-5-(2-methoxyphenoxy)[2, 2â²-bipyrimidin]-4-yl]-2-phenylethenesulfonamide monopotassium salt (YM598), on endothelin-1-induced contractile responses. In the in vitro study, endothelin-1 induced contractile responses in isolated rabbit bladder base, urethra, and prostate tissues. YM598 (10â 7-10â 5 M) antagonized these endothelin-1-induced contractile responses without affecting the maximal responses. In the in vivo study, endothelin-1 induced the elevation of non-prostatic urethral pressure as well as prostatic urethral pressure even in the presence of tamsulosin (10 μg/kg, i.v.) in anesthetized male dogs. YM598 (0.1-3 mg/kg, i.v.) inhibited these endothelin-1-induced contractile responses in a dose-dependent fashion. These results suggest that endothelin ETA receptors play an important role in the lower urinary tract contraction, and that the selective endothelin ETA receptor antagonist YM598 has ameliorating effects on various urinary dysfunctions, including benign prostatic hyperplasia.
Keywords
Related Topics
Life Sciences
Neuroscience
Cellular and Molecular Neuroscience
Authors
Masashi Ukai, Hironori Yuyama, Akira Fujimori, Akiko Koakutsu, Masanao Sanagi, Akiyoshi Ohtake, Shuichi Sato, Katsumi Sudoh, Masao Sasamata, Keiji Miyata,