Role of Nitric Oxide in Fetal Lower Urinary Tract Function

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Abstract
We studied the role of nitric oxide (NO) in normal function of the lower urinary tract in fetal lambs. Fetal surgery was performed in pregnant ewes at 118 days' gestation (term 145-days) to place arterial, venous, and double-lumen urachal catheters. Five animals had a catheter secured in the distal urethra (to measure voided volume), and six underwent ligation of the urethra. Urodynamic studies were performed via the urachal catheter under baseline conditions, during systemic blockade of NO synthesis with N omega-nitro-L-arginine, and with systemic NO stimulation by L-arginine 48 hours postoperatively. Nitric oxide blockade caused an 88% mean increase in bladder capacity (volume to initiation of voiding) (p < 0.001) and a 5.8-fold increase in mean postvoid residual volume (p < 0.0001) despite normal maximal bladder pressures, suggesting inadequate sphincteric relaxation. Qualitatively, NO inhibition increased the presence of low-level bladder contractions and caused a trend toward decreased bladder compliance. Increase of NO substrate by L-arginine infusion restored baseline findings if performed after N omega-nitro-L-arginine. Stimulation of NO by L-arginine infusion caused continuous efflux of the infusate secondary to a persistently open sphincter. In conclusion, NO is active in the function of the lower urinary tract in the fetal lamb and appears to influence both sphincter and detrusor activity.