Age-associated urethral dysfunction in urethane-anesthetized rats

Neurourol Urodyn. 2018 Apr;37(4):1313-1319. doi: 10.1002/nau.23481. Epub 2018 Jan 15.

Abstract

Aims: We aimed to investigate the age-associated changes in movement coordination between the urinary bladder and the urethra in rats.

Methods: A total of 17 female Sprague-Dawley rats were used. The rats were divided into young (3 months old) and middle-aged (12-15 months old) groups. In both groups, isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were performed under urethane anesthesia. After the rhythmic bladder contractions stabilized, L-arginine, a nitric oxide (NO) substrate (100 mg/kg), was administered intravenously in both groups. Subsequently, N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg/kg) was injected intravenously to inhibit NO synthase activity in both groups.

Results: UPP change, defined as UPP nadir minus baseline UPP, was significantly smaller in middle-aged rats (64%) than in young rats (P < 0.05). The mean amplitude of high-frequency oscillations (HFOs) of the external urethral sphincter was also significantly lower (62%) in middle-aged rats than that in young rats (P < 0.05). Urethral contraction during UPP change was also noted in middle-aged rats. This urethral contraction disappeared after L-arginine administration. UPP nadir during bladder contraction was inhibited by L-NAME in both groups. UPP change was greater in middle-aged rats than in young rats, and 3 out of 9 middle-aged rats showed a detrusor-sphincter dyssynergia pattern after L-NAME.

Conclusions: The results indicated that aging induces dysfunction in movement coordination between the urinary bladder and the urethra. Thus, age-associated urethral dysfunctions may lead to inefficient voiding with increased post-void residual urine volume, which is often observed in elderly populations.

Keywords: aging; nitric oxide; urethra.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / physiology*
  • Anesthetics, Intravenous
  • Animals
  • Enzyme Inhibitors / pharmacology
  • Female
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Urethane
  • Urethra / physiopathology*
  • Urinary Bladder Diseases / physiopathology
  • Urination / physiology*

Substances

  • Anesthetics, Intravenous
  • Enzyme Inhibitors
  • Urethane
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester