Non‐Adrenergic, Tamsulosin‐Insensitive Smooth Muscle Contraction is Sufficient to Replace α1‐Adrenergic Tension in the Human Prostate. Issue 7 (24th January 2017) - Hennenberg, Martin
Abstract : BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia may be caused by prostate smooth muscle contraction. Although α1 ‐blockers may improve symptoms by prostate smooth muscle relaxation, their efficacy is limited. This may be explained by non‐adrenergic mediators causing contraction in parallel to α1 ‐adrenoceptors. However, little is known about the relevance and cooperative actions of non‐adrenergic mediators in the prostate. METHODS: Prostate tissues were obtained from radical prostatectomy (n = 127 patients). Contractile responses were studied in an organ bath. RESULTS: Endothelin‐1 and noradrenaline induced contractions of similar magnitude (116 ± 23 and 117 ± 18% of KCl‐induced contractions). Endothelin‐2‐ and ‐3‐induced maximum contractions of 63 ± 8.6 and 71 ± 19% of KCl, while contractions by the thromboxane analog U46619 amounted up to 63 ± 9.4%. Dopamine‐induced contractions averaged to 22 ± 4.5% of KCl, while maximum contractions by serotonin, histamine, and carbachol stayed below 10% of KCl‐induced. While noradrenaline‐induced contractions were inhibited by tamsulosin (300 nM), endothelin‐1‐, ‐2‐, or ‐3‐induced contraction were not. No additive effects were observed if endothelins and noradrenaline were applied consecutively to the same samples. If endothelin‐1 was applied after U46619, resulting tension (172 ± 43% of KCl) significantly exceeded noradrenaline‐induced contraction. Tensions following combined application of endothelin‐2 or ‐3 with U46619 stayed below noradrenaline‐induced contractions. Tension following combined application of all three endothelins with U46619 resembled maximum noradrenaline‐induced tone. CONCLUSIONS: Contractions following concomitant confrontation of human prostate tissue with noradrenaline and endothelin‐1 are not additive. Endothelin‐1 is sufficient to induce a smooth muscle tone resembling that of noradrenaline. This may replace lacking α1 ‐adrenergic tone under therapy with α1 ‐blockers, explaining the limited efficacy of α1 ‐blockers in LUTS treatment. Contractions by thromboxane and endothelin‐1 may be additive, and may exceed α1 ‐adrenergic tone. Prostate 77:697–707, 2017 . © 2017 Wiley Periodicals, Inc.