Chronic Bladder Ischemia Enhances Mechanosensitive Afferent C-Fiber Activity: Insights From a Newly Developed Female...

This study aimed to develop and validate an atherosclerosis-induced chronic bladder ischemia (CBI) model in female rats and to evaluate mechanosensitive single-unit afferent activity (SAA) in bladder-innervating fibers in both male and female CBI models.

Sprague-Dawley rats of both sexes were divided into sham and CBI groups. The CBI group underwent balloon-induced endothelial injury of the iliac arteries and received a 2% cholesterol diet for 8 weeks. Sham rats underwent bilateral inguinal incisions without arterial injury and were fed a regular diet. In female rats, iliac arterial wall thickening, 24-h voiding behavior, cystometric parameters, bladder blood flow, and fibrosis were assessed to evaluate CBI-induced bladder dysfunction. SAAs were recorded under urethane anesthesia. Bladder-innervating fibers were identified via electrical stimulation of the left pelvic nerve and bladder distension. Fibers were classified as Aδ- or C-fibers based on conduction velocity.

Female CBI rats showed thickening of the common iliac arteries, increased voiding frequency, shortened intercontraction intervals, reduced bladder blood flow, and detrusor smooth muscle fibrosis, consistent with previous studies in male rats. In both sexes, the CBI group showed significantly higher SAAs in C-fibers than the sham group. No significant differences were found in SAAs of Aδ-fibers, although there was a tendency for female CBI rats to show higher activity.

This study successfully established arteriosclerosis-induced CBI accompanied by frequent voiding in female rats, similar to males. In addition, the present findings suggest that C-fiber, but not Aδ-fiber, afferent activity is selectively facilitated under CBI conditions.