Abstract
Functional effects of endothelin-1 (ET-1) were investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and human penile circumflex veins (CV). In all preparations, ET-1 induced slowly developing, concentration-dependent contractions. The threshold concentration of ET-1 in CV was approximately 10 and 112 times lower than the threshold concentrations in human and rabbit CC, respectively. Furthermore, the contractions in CV reached a defined maximum at 10(-7) M ET-1 (-log EC50 = 9.12 +/- 0.17), whereas no maximum was obtained in CC preparations within the concentration range used (less than or equal to 3 x 10(-7) M). Pretreatment with the Ca++ channel blocker nimodipine partly reduced the ET-1-induced contractions in human and rabbit CC, but had no significant effect on CV preparations. In a Ca(++)-free medium containing the chelator ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetra-acetic acid, the contractions induced by ET-1 were reduced, but not abolished, in all preparations. The contractions induced by ET-1 are thus mediated mainly by influx of Ca++, although there seem to exist differences in the relative contribution of L-type Ca++ channels in CC and CV. Furthermore, additional mechanisms beside Ca++ influx are likely to be involved in both tissues. A high density of [125I]ET-1 binding sites was observed throughout the stroma and in the muscle layer of the deep penile artery in both human and rabbit CC. In the human CV, numerous binding sites were observed, but no clear difference between the various structures of the vessel wall could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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