Contractile responses in intact and mucosa-denuded human ureter—a comparison with urinary bladder detrusor preparations

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.

A porcine model of ureteral contractile activity: Influences of age, tissue orientation, region, urothelium, COX and NO

“…The present results show that ureteral contraction in response to muscarinic receptor stimulation also differs in tissues from the two age groups. Ureters from the young animals did not respond to carbachol, and this is comparable to results reported for the human ureter (Roedel et al, 2018). In contrast, tissue strips from the older animals generated phasic contractile activity in a concentration-dependent manner to muscarinic receptor stimulation.…”

“…The potent inhibitory effect of the mucosa is present throughout the lower urinary tract including in the bladder and urethra (Sellers, Chess-Williams, & Michel, 2018). In a recent report, phenylephrine-induced contractile responses of the human ureter were depressed in the presence of the urothelium (Roedel et al, 2018). Interestingly, a study on the rat ureter depicted the inhibitory effects of the mucosa on carbachol, angiotensin II and bradykinininduced contractions but not on α 1-adrenoceptor stimulated response (Mastrangelo et al, 2000).…”

Activation of TRPM8 channel inhibits contraction of the isolated human ureter

“…Ureter mucosa plays an important role in the regulation of ureter contraction 10 . To examine the role of the mucosa, menthol and icilin induced changes were examined in mucosa‐denuded ureter strips.…”

“…Ureter mucosa plays an important role in the regulation of ureter contraction. 10 To examine the role of the mucosa, menthol and icilin induced changes were examined in mucosa-denuded ureter strips. Compared with the responses in intact ureters, menthol or icilin evoked reduction in contraction frequency was significantly decreased in mucosa-denuded strips (Figure 2A,B).…”

Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium

“…Even less well researched is the urothelium of the ureter, although recent evidence suggests that it can influence the underlying smooth muscle in a manner similar to that seen in the bladder dome, trigone and urethra (Roedel et al, 2018).The urothelium in the human ureter can inhibit tonic, but not spontaneous or KCl-stimulated contractions. In the rat ureter the urothelium acts to prevent spontaneous contractile activity and also decrease potential excitatory effects of endogenous contractile agents including carbachol, bradykinin and angiotensin II on ureteral motility (Mastrangelo and Iselin, 2007).…”