Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding

Area of Science:

• Urology
• Neuroscience
• Physiology

Background:

• Elevated nerve growth factor (NGF) in bladder smooth muscle cells (BSMCs) is linked to hyperactive voiding.
• Spontaneously hypertensive rats (SHRs) exhibit both hypertension and behavioral hyperactivity, with increased BSMC NGF secretion.

Purpose of the Study:

• To investigate the relationship between NGF secretion, hypertension, and hyperactivity using inbred rat strains.
• To determine if NGF secretion patterns correlate with specific phenotypes (hypertensive vs. hyperactive).

Main Methods:

• Compared basal and inhibited NGF secretion in BSMCs from WKHT (hypertensive) and WKHA (hyperactive) rat strains.
• Measured bladder norepinephrine content and voiding frequency across different rat strains.
• Investigated the effect of Protein Kinase C (PKC) agonists on NGF production.

Main Results:

• WKHA BSMCs showed higher basal NGF secretion than WKHT BSMCs.
• NGF secretion was inhibited by antagonists in WKHA but not WKHT cultures.
• Bladder norepinephrine content varied across strains, correlating with NGF levels.
• Voiding frequency differed significantly between strains, with SHRs exhibiting the highest frequency.

Conclusions:

• Augmented basal NGF secretion is associated with hyperactivity, while lack of inhibition correlates with hypertension.
• Altered PKC signaling may contribute to strain-specific differences in NGF secretion.
• Both hypertensive and hyperactive phenotypes may contribute to elevated SHR bladder NGF and overactive voiding.