Abstract
In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.
Highlights
Contraction and relaxation of smooth muscle cells (SMCs) of the ureter are responsible for active propulsion of urine from the kidneys to the bladder by peristalsis
Average SMC density was between 8 cells per 104 mm2 and 25 cells per 104 mm2
Our high-resolution data was obtained in intact ureters by using two-photon laser scanning microscopy (TPLSM), an imaging technique similar to confocal laser scanning microscopy (CLSM) [29]
Summary
Contraction and relaxation of smooth muscle cells (SMCs) of the ureter are responsible for active propulsion of urine from the kidneys to the bladder by peristalsis. It is accepted that orientation of SMCs plays an important role in peristalsis [1], morphological reports on the lamina muscularis (LM) are inconsistent. Findings with respect to the number of layers that are distinguishable by orientation and with respect to the specific orientation of SMCs within the layers (circumferential, longitudinal, helical, disperse) differ between studies. A number of investigators reported different layers in the LM of human ureters based on distinct SMC orientation patterns [2,3,4,5,6,7,8,9], whereas others did not find a well-defined layering in SMC orientations [10,11,12,13,14,15,16,17,18,19]. Most studies evaluated the LM’s structure by histological sectioning methods, which may affect tissue morphology and provides limited capabilities for quantifying SMC orientation across the thickness of the LM
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