Frontiers in Physiology (May 2025)

Voiding symptom severity varies independently from non-adrenergic prostate smooth muscle contractions in patients undergoing surgery for benign prostatic hyperplasia

  • Patrick Keller,
  • Sheng Hu,
  • Philip Nicola,
  • Laurenz Berger,
  • Alexander Tamalunas,
  • Philipp Weinhold,
  • Christian G. Stief,
  • Martin Hennenberg

DOI
https://doi.org/10.3389/fphys.2025.1612954
Journal volume & issue
Vol. 16

Abstract

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BackgroundResistance of voiding symptoms to α1-blockers in benign prostatic hyperplasia (BPH) has been provisionally explained by non-adrenergic prostate smooth muscle contraction. Here, we examined relationships between contractions and voiding symptoms in prostate tissues from laser-enucleation.MethodsTissues were obtained from holmium and thulium laser enucleation. Contractions were induced by endothelin-1, U46619, noradrenaline and electric field stimulation (EFS). Emax values were analyzed for correlation with international prostate symptom score (IPSS), and compared to tissues from patients without surgery for BPH.ResultsNoradrenaline- and EFS-induced contractions were higher with severe (IPSS 20–35) than moderate symptoms (IPSS 8–19) (Emax noradrenaline 66% vs 113% of KCl-induced contractions; EFS 33% vs 66%). Endothelin-1- and U46619-induced contractions were already maximum with moderate symptoms (endothelin-1 117% moderate, 135% severe; U46619 23%, 27%). Within 8–21 points, IPSS increased with Emax values for noradrenaline and EFS (r = 0.545, r = 0.448), but not with endothelin-1- or U46619-induced contractions. Endothelin-1-induced contractions were similar to noradrenaline-induced contractions (Emax endothelin-1 126% of KCl, noradrenaline 96%), and exceeded EFS- (52%) and U46619-induced contractions (25%). Emax values for endothelin-1 were similar between laser-enucleated patients and patients without surgery for BPH (127%), while Emax values for U46619 were higher in tissues from patients without surgery for BPH (59%) compared to laser-enucleated tissues.ConclusionSymptom severity increases with α1-adrenergic, but not with non-adrenergic contractions in patients undergoing surgery for BPH. Endothelin-1-induced contractions are similar to noradrenaline-induced contractions. Conditions necessitating BPH surgery may not necessarily depend on α1-adrenergic tone, but may involve non-adrenergic contractions or factors beyond contraction.

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