Objectives:
Sympathetic innervation mediates tonic contraction of proximal urethral smooth muscle, thus contributing to urinary continence. Urethral innervation is particularly susceptible to damage during vaginal delivery, a time characterized by decreasing estrogen levels. Because regeneration of other nerves types can be influenced by estrogen, the present study was conducted to assess whether sympathetic reinnervation of the rat proximal urethra is affected by differences in estrogen levels.
Methods:
Adult female rats were ovariectomized and implanted with pellets containing vehicle or estrogen to achieve serum levels similar to rodent pregnancy. Rats were injected intravenously with vehicle or the selective sympathetic neurotoxin 6-hydroxydopamine, which produces uniform and complete destruction of terminal sympathetic axons. At 1, 4, 12 and 25 days, tyrosine hydroxylase-immunoreactive sympathetic innervation of the proximal urethral smooth muscle was assessed quantitatively.
Results:
In rats with intact innervation, the proximal urethra is densely innervated, and nerve density is comparable irrespective of estrogen status. 6-Hydroxydopamine induced marked sympathetic axon disruption by 1 day and complete denervation by 4 days post-injection in ovariectomized rats receiving vehicle or estrogen. In vehicle-treated rats, few nerves were present at 12 days post-sympathectomy, and innervation remained substantially below normal levels at 25 days. In estrogen-treated rats, sympathetic reinnervation was 2-fold greater at 12 days, and by 25 days was comparable to controls.
Conclusion:
Estrogen improves sympathetic reinnervation of the proximal urethra. Estrogen titers in individuals with urethral sympathetic nerve damage may therefore influence the rate and extent of urethral smooth muscle reinnervation.