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Abstract
Purpose
We investigated the effects of estrogen on the expression of neuronal nitric oxide synthase (nNOS) and on endothelial nitric oxide synthase (eNOS), and furthermore elucidated its effect on the histologic composition of the rat bladder and urethra.
Materials and Methods
Forty-five mature female Sprague-Dawley rats (10-11 weeks, 235-250g) were randomly assigned to one of three groups: control group (C), oophorectomy group (O), or hormone (estradiol) replacement group (H). The degree of expression of nNOS and eNOS in bladder and urethral tissues was investigated using immunohistochemical staining, and tissue was described as mucosa, smooth muscle, or vessel. We also investigated changes in histologic composition using Masson's trichrome stain.
Results
In bladder and urethra, the expression rates of nNOS and eNOS significantly increased in the O group, but decreased in the H group (p＜ 0.05), except for nNOS in the mucosa and smooth muscle of the bladder. The relative collagen ratios significantly increased in bladder and urethra in the O group, to 121.2±12.7% and 135.5±25.2%, respectively, but decreased to 95.6±15.2% and 93.7±12.8% in the H group, respectively (p＜0.05).
REFERENCES
1. Iosif CS, Bekassy Z, Rydhstrom H. Prevalence of urinary incontinence in middle-aged women. Int J Gynaecol Obstet. 1988; 26:255–9.
2. Takahashi W, Yoshida M, Wada Y, Goto S, Inadome A, Yono M, et al. Effect of estrogen on nitric oxide-induced relaxation of the rabbit urethra. Eur J Pharmacol. 1997; 339:165–71.
3. Dokita S, Morgan WR, Wheeler MA, Yoshida M, Latifpour J, Weiss RM. NG-nitro-L-arginine inhibits non-adrenergic, non-cholinergic relaxation in rabbit urethral smooth muscle. Life Sci. 1991; 48:2429–36.
4. Hashimoto S, Kigoshi S, Muramatsu I. Nitric oxide-dependent and -independent neurogenic relaxation of isolated dog urethra. Eur J Pharmacol. 1993; 231:209–14.
5. Leone AM, Wiklund NP, Hokfelt T, Brundin L, Moncada S. Release of nitric oxide by nerve stimulation in the human urogenital tract. Neuroreport. 1994; 5:733–6.
6. Yallampalli C, Byam-Smith M, Nelson SO, Garfield RE. Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus. Endocrinology. 1994; 134:1971–4.
7. Hextall A. Oestrogens and lower urinary tract function. Maturitas. 2000; 36:83–92.
8. Ingelman-Sundberg A, Rosen J, Gustafsson SA, Carlstrom K. Cytosol estrogen receptors in the urogenital tissues in stress-incontinent women. Acta Obstet Gynecol Scand. 1981; 60:585–6.
9. Hextall A, Cardozo L. The role of estrogen supplementation in lower urinary tract dysfunction. Int Urogynecol J Pelvic Floor Dysfunct. 2001; 12:258–61.
10. Rand MJ, Li CG. Discrimination by the NO-trapping agent, carboxy-PTIO, between NO and the nitrergic transmitter but not between NO and EDRF. Br J Pharmacol. 1995; 116:1906–10.
11. Bennett BC, Kruse MN, Roppolo JR, Flood HD, Fraser M, de Groat WC. Neural control of urethral outlet activity in vivo: role of nitric oxide. J Urol. 1995; 153:2004–9.
12. Al-Hijji J, Batra S. Downregulation by estrogen of nitric oxide synthase activity in the female rabbit lower urinary tract. Urology. 1999; 53:637–41.
13. Shapiro E. Effect of estrogens on the weight and muscarinic cholinergic receptor density of the rabbit bladder and urethra. J Urol. 1986; 135:1084–7.
14. Larsson B, Andersson KE, Batra S, Mattiasson A, Sjogren C. Effects of estradiol on norepinephrine-induced contraction, alpha adrenoceptor number and norepinephrine content in the female rabbit urethra. J Pharmacol Exp Ther. 1984; 229:557–63.
15. Fantl JA, Wyman JF, Anderson RL, Matt DW, Bump RC. Postmenopausal urinary incontinence: comparison between non-estrogen-supplemented and estrogen-supplemented women. Obstet Gynecol. 1988; 71:823–8.
16. Jackson S, Shepherd A, Brookes S, Abrams P. The effect of oestrogen supplementation on postmenopausal urinary stress incontinence: a double-blind placebo-controlled trial. Br J Obstet Gynaecol. 1999; 106:711–8.
17. Beisland HO, Fossberg E, Moer A, Sander S. Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation. Urol Int. 1984; 39:211–6.
18. Ho MH, Bhatia NN, Khorram O. Physiologic role of nitric oxide and nitric oxide synthase in female lower urinary tract. Curr Opin Obstet Gynecol. 2004; 16:423–9.
19. Chertin B, Rolle U, Solari V, Cascio S, Puri P. The role of nitric oxide in bladder urothelial injury after bladder outlet obstruction. BJU Int. 2004; 94:392–9.
20. Aikawa K, Chichester P, Whitbeck C, Levin RM. Effect of nitric oxide synthase inhibition on changes induced by estradiol in bladders from ovariectomized rabbits. Urol Int. 2005; 75:133–8.
Fig. 1.
The mean expression percentage of neuronal nitric oxide synthase (nNOS). A: bladder, B: urethra. Control: control group, Ox: oophorectomy group, HRT: hormone replacement group, ∗: p＜0.05 vs control group, †: p＜0.05 vs oophorectomy group.
Fig. 2.
Immunoreactivity pattern for neuronal nitric oxide synthase (nNOS) in rat bladder and urethra. (A) control group, (B) oophorectomy group, (C) hormone replacement group (x200).
Fig. 3.
Mean expression percentage of endothelial nitric oxide synthase (eNOS). A: bladder, B: urethra, Control: control group, Ox: oophorectomy group, HRT: hormone replacement group, ∗: p＜0.05 vs control group, †: p＜0.05 vs oophorectomy group.
Fig. 4.
Immunoreactivity pattern for endothelial nitric oxide synthase (eNOS) in rat bladder and urethra. (A) control group, (B) oophorectomy group, (C) hormone replacement group (x200).
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