Nitric oxide synthase and the lower urinary tract: possible implications for physiology and pathophysiology

Area of Science:

• Urology
• Neuroscience
• Pharmacology

Background:

• Non-adrenergic, non-cholinergic (NANC) nerves mediate relaxation in the lower urinary tract.
• L-arginine-derived nitric oxide (NO) is the primary mediator of this NANC response.
• Nitric oxide synthase (NOS) is localized in nerve fibers throughout the lower urinary tract, particularly in the outflow region.

Purpose of the Study:

• To investigate the role of the L-arginine/NO system in lower urinary tract function.
• To determine the functional significance of NO in detrusor and urethral smooth muscle.
• To explore the potential involvement of NO in afferent neurotransmission and voiding control.

Main Methods:

• Localization studies of NOS in lower urinary tract tissues.
• Assessment of NO's relaxant effects on isolated smooth muscle preparations.
• Investigation of NO's role in modulating neurotransmission and afferent activity.

Main Results:

• NOS is localized in nerve fibers of the detrusor, trigone, and urethra, with higher density in the outflow region.
• NO effectively relaxes smooth muscle from the urethral outflow region, suggesting a role in decreasing intraurethral pressure during micturition.
• The detrusor shows low sensitivity to NO, making its role as a primary relaxant neurotransmitter less likely, though modulation of other transmitters is possible.
• The L-arginine/NO system may influence afferent activity in the outlet region, potentially affecting bladder instability.

Conclusions:

• NO plays a significant role in relaxing urethral smooth muscle, contributing to normal micturition and potentially addressing voiding disturbances.
• The functional importance of the L-arginine/NO system in central and peripheral micturition pathways requires further investigation.
• NO may modulate detrusor function and participate in afferent neurotransmission within the lower urinary tract.