Inhibition of Hyperreflexia by Vaginally Administered Oxybutynin: A Novel Rabbit Model

Abstract

The rabbit has proved to be an excellent model in which to study lower urinary tract function and pathological mechanisms involved in specific forms of lower urinary tract dysfunctions, including those involved with partial outlet obstruction (benign prostatic hyperplasia), erectile dysfunction, bladder instability and ischemic bladder disease. The current study describes a model of bladder instability induced in female rabbits and its use in developing a novel form of vaginal treatment for this instability. A total of 18 female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder neck to prevent leakage through the urethra and generate unstable bladder contractions. After initial cystometry the bladder was emptied and then filled to 30 ml. Acetylcholine (Ach) was administered into the vesical artery at 15-minute intervals for 2 hours. Hyperreflexia usually developed within 30 minutes. Vaginal oxybutynin (low and high dose) was applied and the effect on cystometry, the response to Ach, and the amplitude and frequency of hyperreflexia was determined. Each dose of oxybutynin increased bladder capacity and improved compliance. The high oxybutynin dose completely inhibited the response to Ach and significantly decreased micturition pressure. The high dose decreased uninhibited bladder contraction peak pressure in a time dependent manner to a greater extent than it decreased uninhibited contraction frequency. The low dose of oxybutynin had no effect on micturition pressure, significantly inhibited the response to Ach and hyperreflexia amplitude to approximately 40% of control values, and had little effect on hyperreflexia frequency. Vaginally delivered oxybutynin was effective in improving bladder compliance, inhibiting intra-arterial Ach stimulated bladder contractions and significantly decreasing the amplitude of hyperreflexia. Vaginal oxybutynin had a more potent effect on the evoked response to Ach and on hyperreflexia than it did on micturition pressure.