Abstract
Human proximal and distal ureter tissues were studied to clarify whether the presence of mucosa affects contractile responses. In histological studies, human ureter was compared with urinary bladder (detrusor). Contractions in response to high KCl solution, phenylephrine, and carbachol were measured in intact and mucosa-denuded strips of human ureter. Tissue sections of human bladder and ureter were used for histological staining. Thirty-four percent of the ureter strips contracted spontaneously with highly variable patterns, and this was affected neither by mucosa nor by proximal or distal tissue origin. Upon stimulation with 40 mM KCl, ureter strips exhibited strong phasic and weak tonic contractions. In intact strips, normalized tonic force was lower than in denuded strips, but no consistent effect of mucosa was observed with phasic contractions. Absolute force values of phasic contractions were weaker in proximal than distal ureter strips, but similar when normalized to tissue wet weight. Stimulation with 80 mM KCl enhanced tonic contraction fourfold; phasic contractions occurred rarely. Phenylephrine produced no statistically significant stronger tonic contraction in distal compared with proximal ureter strips; nevertheless, in some strips, pre-existing spontaneous contractions increased. Carbachol did not influence ureter contractions. In the bladder, a suburothelial cell layer stained positive with α-smooth muscle actin (α-SMA)-specific antibodies could be further differentiated with vimentin- and desmin-specific antibodies. α-SMA positive cells were absent in suburothelial ureter tissue. Like in detrusor, the mucosa inhibits KCl-stimulated tonic ureter contractions. The mucosa of detrusor and ureter tissue exhibits distinct staining patterns for α-SMA, vimentin, and desmin. This suggests a different distribution of smooth muscle cells, fibroblasts, and myofibroblasts, which could be a target for pharmacological therapy of pathologic contractile processes.
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The authors gratefully acknowledge the team of the Clinic of Urology, University Hospital Carl Gustav Carus Dresden for providing the tissue samples used for this study.
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Supplementary Fig. 1
A: Distal ureteral strip, cut open longitudinally. B: Larger magnification on the right side showing fine spider-like vessels of the mucosa. Scale bar, left 4 mm, right 1 mm. C and D: Hematoxylin-Eosin staining of distal ureter strips, intact (C) and without mucosa (D). 1: Urothelium; 2: Lamina propria, 2a: transition from lower rim of lamina propria and smooth muscle; 3: smooth muscle. (PNG 767 kb)
Supplementary Fig. 2
Correlation between wet weight (mg) of ureteral strips and maximum phasic and tonic force in response to 40 mM KCl. All values for phasic force ≥1.0 mN and tonic force ≥0.5 mN included. Correlation coefficient (r2) and P value for significantly difference from slope zero is given for each group. A + C: Proximal strips (with and without mucosa); B + D: Distal strips (with and without mucosa). (PNG 47 kb)
Supplementary Fig. 3
Maximum phasic and tonic force development of human ureteral strips exposed to 40 mM KCl. A: Bar graphs (means ± SD): same values as for Fig. 2, but P values given for difference between proximal and distal strips. B: Scatter plots contain all values for phasic force ≥1 mN and tonic force ≥0.5 mN. P values for comparison of proximal versus distal strips. (PNG 115 kb)
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Roedel, M., Ravens, U., Kasper, M. et al. Contractile responses in intact and mucosa-denuded human ureter—a comparison with urinary bladder detrusor preparations. Naunyn-Schmiedeberg's Arch Pharmacol 391, 773–782 (2018). https://doi.org/10.1007/s00210-018-1505-5
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DOI: https://doi.org/10.1007/s00210-018-1505-5