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Analysis of Changes in Nitric Oxide Synthase Signaling in BB/WOR Diabetic Prostate

Carol A Podlasek, Christopher W Bond, Yi Tang, Lance Marr, Nicholas Angeloni, Douglas Wood, Kevin E McKenna and Kevin T McVary

Purpose: Diabetes is associated with increased lower urinary tract symptom (LUTS) severity. An underlying cause of LUTS is increased prostate smooth muscle tone. A critical regulator of prostate innervation and tone is nitric oxide (NO), produced by nitric oxide synthase (NOS). Since NO regulates proliferation and relaxation, and NOS signaling is altered in patients with LUTS, we propose that decreased NO in diabetic patients leads to increased LUTS. We examined this hypothesis by quantifying changes in NOS signaling in the BB/WOR diabetic rat prostate.

Materials and Methods:Protein and RNA abundance and localization of NOS I, -II and -III were examined in control and diabetic BB rat prostate by Real time RT-PCR, Western, immunohistochemical analysis and in situ.Morphological changes were examined by electron microscopy (EM), and TUNEL.

Results:NosIII is the most abundant isoform in ventral and dorsal prostate. NOS I, -II and -III protein and RNA localize to ductal epithelium. NOS III protein and RNA were significantly decreased in diabetic prostate. Apoptosis was increased in diabetic dorsal prostate. EM of the diabetic dorsal prostate showed abundant protein filled vacuoles and abnormal cytoplasmic morphology indicative of apoptosis.

Conclusions:Since NOS III is the most abundant form of NOS in the prostate diabetes may contribute to LUTS severity by down regulating NO, which may lead to increased proliferation in ductal epithelium