Estrogen administration attenuates bladder outlet obstruction induced oxidative stress in the female rabbit.

AIMS: Estrogen administration to female rabbits induces a functional hypertrophy of the bladder. The aim of this study was to investigate whether supplementation of estrogen in the female rabbit with partial bladder outlet obstruction (PBOO) would affect the severity of bladder dysfunction. METHODS: We surgically created PBOO in female New Zealand White rabbits. Group 1 included sham operated rabbits which served as controls. Group 2 received PBOO without estrogen treatment. Group 3 received estrogen treatment after PBOO. Group 4 received estrogen pretreatment before PBOO. The bladders were then removed for contractile, biochemical, and protein expression studies. There were four rabbits per group. RESULTS: (1) PBOO resulted in significant decreases in the contractile responses to all forms of stimulation (field stimulation [FS], carbachol, KCl, ATP). Both pretreatment and post-treatment with estrogen resulted in significantly increased contractile responses to all forms of stimulation, although the responses were still lower than control. (2) PBOO resulted in a significant decrease in the activity of choline acetyltransferase (ChAT). Both pretreatment and post-treatment with estrogen resulted in significant increases in ChAT activity back toward control levels. (3) PBOO resulted in significant increases in both protein oxidation and nitration; both pretreatment and post-treatment with estrogen significantly reduced oxidation and nitration toward control levels. CONCLUSIONS: Estrogen pretreatment and post-treatment in the female rabbit ameliorated contractile and biochemical dysfunctions associated with PBOO. This improvement is likely due to reduced oxidative stress. As expected, pretreatment was generally more effective than post-treatment.

Effect of castration on male rabbit lower urinary tract tissue enzymes.

OBJECTIVES: The influence of testosterone on the prostate and corpus cavernosum have been studied extensively. However, the influence of testosterone on the lower urinary tract (bladder and urethra) have not been investigated to any great extent. The aim of this study was to determine whether androgen deprivation alters lower urinary tract metabolism. METHODS: A total of 16 rabbits were divided into four groups of four rabbits each. Each rabbit in groups 1-3 underwent surgical bilateral castration for duration of 1, 2 , and 4 weeks, and group 4 underwent sham operations. Sections of bladder body and base wall and mucosa, urethra and corpora were isolated, frozen, and stored under liquid nitrogen. The activities of citrate synthase-thapsigargin sensitive Ca(2+) ATPase (Sarco/Endoplasmic Reticulum Ca(2+ )ATPase [SERCA]), and choline acetyl-transferase were examined as markers for mitochondrial function, sarcoplasmic reticular calcium storage and release, and cholinergic nerve function, respectively. RESULTS: The activity of SR function indicator, Ca(2+) ATPase was significantly higher in the control corpora than in the control bladder or urethra. Castration resulted in decreased activity in the mitochondria specific enzyme, citrate synthase, the activity of which was greatest in the urethra and lowest in the corpora. Cholinergic nerve density indicator, choline acetyl-transferase activity was greatest in the bladder body and lowest in the urethra. CONCLUSIONS: Our data indicate that (1) significant differences exist in the activities of all three enzymes in the various organs associated with the lower urinary tract; and (2) that castration results in significant alterations in the activities of all three enzymes in the bladder body, base, urethra, and corpora.

Role of nitric oxide in urinary bladder function: effect of L-arginine.

BACKGROUND: Evidence indicates that decreased blood flow to the bladder plays a major role in obstructive bladder dysfunction in the rabbit model of partial bladder outlet obstruction (PBOO), and that nitric oxide (NO) regulation of blood flow may be important in modulating the degree of obstructive bladder dysfunction. The specific aim of our study is to determine the effect of feeding rabbits a diet high in L-arginine on the response to PBOO. MATERIALS AND METHODS: Sixteen male NZ White rabbits were separated into 4 groups of 4 each. The rabbits in groups 1 and 3 underwent PBOO. The rabbits in groups 2 and 4 were sham-operated. For 1 week prior to surgery, and 2 weeks postoperatively, each rabbit in groups 1 and 2 was put on a diet containing 7% arginine. Rabbits in groups 3 and 4 were on a normal diet (0.76% arginine). RESULTS: PBOO resulted in a greater increase in bladder weight in the control group than the arginine group. PBOO resulted in a greater decrease in compliance in the control group than the arginine group. The contractile responses to all agents in the arginine control group were greater than in the control normal diet group. PBOO resulted in a greater decrease in the response to field stimulation in the control group than in the arginine group. CONCLUSIONS: These studies clearly demonstrate that feeding rabbits a diet high in L-arginine was beneficial for the control rabbits, and reduced the level of dysfunctions following PBOO.

Estrogen induced functional hypertrophy and increased force generation of the female rabbit bladder.

AIMS: Estrogen is essential for physiological maintenance of the female urogenital tract. It is believed that alterations in female sex hormones play a major role in the etiology and response to urinary tract dysfunctions. In animal studies, ovariectomy (Ovx) results in smooth muscle (SM) weakness and atrophy whereas estrogen supplementation reverses these effects. Our study seeks to establish the mechanisms by which estrogen augmentation results in increased contractility. METHODS: Twenty New Zealand White female rabbits were separated into five groups of four each. Group 1 served as control, rabbits of groups 2-5 were ovariectomized, group 2 ovariectomized received no estradiol, groups 3-5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous slow release tablet implant for 1, 3, and 7 days, respectively, beginning 2 weeks after Ovx. At the end of the experimental period, each rabbit was anesthetized and the urinary bladder was removed for contractile, histological, and biochemical studies. RESULTS: Ovx resulted in significantly decreased bladder contractile function, whereas bladders tested after estradiol administration showed increased contractility. Ovx resulted in a decrease in SM/collagen ratio, whereas estrogen resulted in an increase. The estrogen receptor (ER) density significantly increased following Ovx. After 1 day of estrogen treatment, the ER density decreased significantly below control levels, but rose progressively during the estrogen treatment. CONCLUSION: The present study demonstrates that estrogen supplementation mediates a "functional hypertrophy," that is a hypertrophy characterized by increased contractile responses to all forms of stimulation, and an increased ratio of SM/collagen.

Protection of urinary bladder function by grape suspension.

Urinary bladder dysfunction secondary to BPH is a major affliction of aging men. A rabbit model of partial outlet obstruction was used to evaluate the ability of a standardized grape suspension to protect the bladder against obstructive bladder dysfunction.Twenty-four New Zealand White rabbits were separated into four groups of six rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with a standardized grape suspension suspended in water; groups 2 and 4 were treated with vehicle. Groups 1 and 3 received sham operations after 3 weeks of treatment; groups 2 and 4 received partial outlet obstruction by surgically placing a silk ligature loosely around the urethra. At 3 weeks following surgery, in vivo and in vitro bladder functions were evaluated. Based on both in vivo and in vitro studies, the grape suspension significantly reduced the severity of obstructed bladder dysfunction. This is consistent with the hypothesis that ischemia is a major etiological factor in obstructive dysfunction, and treatment with antioxidants and membrane stabilization compounds such as those in the grape suspension can be effective in the treatment of obstructive bladder pathology.