Decreased Microvascular Density and Nitric Oxide Synthase as Possible Underlying Mechanisms in Children with UPJ Obstruction

Abstract Purpose Nitric oxide plays a significant role in the relaxation process of ureteral, bladder and prostatic smooth muscle cells. Reduced nitric oxide synthase (NOS) activity has been identified as one of the underlying causes in pyloric stenosis and Hirschsprung's disease. We investigated endothelial constitutive NOS and inducible NOS expression as well as microvascular supply in children with UPJ obstruction. Material and Methods 21 UPJ specimens obtained at the time of dismembered pyeloplasty as well as age matched specimens without any history of urological disease were evaluated immunohistochemically. Routine histological paraffin-embedded sections were immunostained to detect eNOS and iNOS and morphologically analyzed. Additionally the vascular density was estimated as the number of positively stained blood vessels/HPF. Furthermore smooth muscle architecture and collagen profile were determined with alpha-SMA and collagen III, respectively. Mann-Whitney U test was used for statistical analysis. Results UPJ specimens displayed a deranged smooth muscle cells distribution and were replaced by connective tissue. eNOS immunoreactivity in obstructed UPJ segments was notably reduced compared to healthy controls. In obstructed UPJ segments immunoreactivity to eNOS was abundant in vessels but little in muscular layers. In the case of iNOS expression, there was no statistical difference between the two groups whereas microvessel density in children with UPJ obstruction was considerably lower than in healthy controls. Conclusions Obstructed UPJ segments were found to have decreased eNOS expression as well as diminished vascular density. These alterations may serve as one of the underlying causes in UPJ obstruction.