Increased expression of neuronal nitric oxide synthase in bladder afferent cells in the lumbosacral dorsal root ganglia after chronic bladder outflow obstruction.
Nitric oxide (NO), a neurotransmitter in autonomic reflex pathways, plays a role in functional neuroregulation of the lower urinary tract. Upregulation of the levels of neuronal nitric oxide synthase (nNOS), the enzyme system responsible for NO synthesis, has been documented in the peripheral, spinal and supraspinal segments of the micturition reflex in diseases such as cystitis, bladder/sphincter dyssynergia following spinal cord injury and bladder overactivity after cerebral infarction. These observations suggest that NO might play a role in the development of bladder overactivity. In this study, nNOS-immunoreactivity (IR) was evaluated in bladder afferent and spinal neurons following bladder outflow obstruction (BOO) in male and female rats. Chronic BOO was induced by placing lumen reducing ligatures around the proximal urethra. Six weeks following the obstructive or sham surgery, bladder function was evaluated by awake cystometry. Bladder afferent neurons in L1, L2, L6 and S1 dorsal root ganglia (DRG) were identified by retrograde neuronal labeling with injection of Fast Blue into the bladder smooth muscle. A differential distribution of nNOS-IR was subsequently evaluated in bladder afferent neurons in the DRG and in the associated spinal cord segments. The percentage of bladder afferent neurons expressing nNOS-IR was increased in L6 (1.8-fold in males and 1.9-fold in females) and S1 (2.8-fold in males and 5.3-fold in females) DRG. In contrast, no changes in nNOS-IR in neurons or fiber distribution were observed in any spinal cord segments examined.
Department of Surgery, University of Vermont, D319 Given Bldg, 89 Beaumont Ave., Burlington, VT 05405, USA. peter.zvara@uvm.edu
Peter
P
Zvara
Jeffrey B
JB
Folsom
Ján
J
Kliment
Abbey L
AL
Dattilio
Adriana
A
Moravcíková
Mark K
MK
Plante
Margaret A
MA
Vizzard
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008161:Lumbosacral Region; D008297:Male; D009475:Neurons, Afferent / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000201:enzymology*; D001748:Urinary Bladder Neck Obstruction / Q000201:enzymology*
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat