Korean J Androl.  2011 Apr;29(1):27-32. 10.5534/kja.2011.29.1.27.

Changes of Endothelin-1 in Rats Corpus Cavernosum Smooth Muscle of Partial Bladder Outlet Obstruction

• Kim KH
• Seo YJ
• Lee KS

• KMID: 2298623
• DOI: http://doi.org/10.5534/kja.2011.29.1.27

Abstract

PURPOSE
Lower urinary tract symptoms and erectile dysfunction (ED) are common disorders in men and increase with age. Recently, there has been evidence to suggest that patients with high benign prostatic hyperplasia symptom scores have an increased frequency of ED. This study was performed to evaluate the change of the expression of endothelin-1 (ET-1) in the corpus cavernosum by inducing partial bladder outlet obstruction (PBOO) in a rat model.
MATERIALS AND METHODS
Eight Sprague-Dawley male rats were used for induction of PBOO by placing a 25 gauge angioneedle sheath around the urethra, then ligating the bladder neck with 3-0 vicryl suture and six sham-operated rats were ligated very loosely without causing obstruction. At three and five weeks after PBOO, the distal portion of the ligated penile tissues was dissected for immunohistochemical staining of ET-1 in the vascular endothelial cell.
RESULTS
ET-1 was weakly expressed (+) in the smooth muscle layers of the control group and a very strong expressed (++++) in the experimental group on 3 weeks after PBOO. However, there was no expression in the experimental group on 5 weeks after PBOO. There was no expression (-) in the vascular endothelial cells of the control group and very strong expression (++++) in the experimental group on 3 weeks after PBOO. Howerver, there was no expression in the experimental group on 5 weeks after PBOO.
CONCLUSIONS
The changes of penis by inducing partial bladder outlet obstruction in the rats were associated with increased ET-1 in the vascular and peri-vascular smooth muscle cells of the corpus cavernosum.

Keyword

Urinary bladder neck obstruction; Erectile dysfunction; Endothelin-1

MeSH Terms

Animals
Endothelial Cells
Endothelin-1
Erectile Dysfunction
Humans
Lower Urinary Tract Symptoms
Male
Muscle, Smooth
Myocytes, Smooth Muscle
Neck
Penis
Polyglactin 910
Prostatic Hyperplasia
Rats
Sutures
Urethra
Urinary Bladder
Urinary Bladder Neck Obstruction
Endothelin-1
Polyglactin 910

Figure

• 

  Fig. 1. The change of bladder outlet weight in the controls and partial bladder outlet obstruction. The bladder weight of the PBOO group was significantly higher than that of control group. ∗p＜0.05 as compared with control, PBOO: partial bladder outlet obstruction.

• 

  Fig. 2. Immunohistochemical identification of endothelin-1 (ET-1) in corpus cavernosum of the penis. The immunoreactivity of the ET-1 showed in the smooth muscle (A) and endothelium of the small vessels (B) in the corpus cavernosum, indicating that the expression of ET-1 was not restricted to the endothelium of the small blood vessels in the corpus cavernosum. In the rats with PBOO treatment for 3 weeks, the density of ET-1 immunoreactive smooth muscle cells and endothelium was significantly up-regulated (++++) compared with those of the control animals while ET-1 level was completely down-regulated in the rats with PBOO treatment for 5 weeks. Sham: sham-operated animals, Csm: smooth muscles of corpus cavernosum, Cbv: small blood vessels of the corpus cavernosum, PBOO 3W: surgical treatment of the PBOO for 3 weeks, PBOO 5W: surgical treatment of the PBOO for 5 weeks, respectively. Scale bar: 50μm.

Reference

1). Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151:54–61.

2). Namasivayam S, Minhas S, Brooke J, Joyce AD, Prescott S, Eardley I. The evaluation of sexual function in men presenting with symptomatic benign prostatic hyperplasia. Br J Urol. 1998; 82:842–6.

3). Roehrborn CG. The prevalence of sexual dysfunction in patients with BPH. Presented at the 13th congress of the Europeam Association of Urology, March 1998, Barcelona.

4). Anderson KE. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev. 1993; 45:253–308.

5). Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Machtens SA, et al. Systemic and cavernous plasma levels of vasoactive intestinal polypeptide during sexual arousal in healthy males. World J Urol. 2002; 20:59–63.

6). Huggins JP, Pelton JT, Miller RC. The structure and specificity of endothelin receptors: their importance in physiology and medicine. Pharmacol Ther. 1993; 59:55–123.

7). Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999; 281:537–44.

8). Braun MH, Sommer F, Haupt G, Mathers MJ, Reifenrath B, Engelmann UH. Lower urinary tract symptoms and erectile dysfunction: co-morbidity or typical "Aging Male" symptoms? Results of the "Cologne Male Survey". Eur Urol. 2003; 44:588–94.

9). Musicki B, Burnett AL. eNOS function and dysfunction in the penis. Exp Biol Med. 2006; 231:154–65.

10). Chang S, Hypolite JA, Zderic SA, Wein AJ, Chacko S, Disanto ME. Increased corpus cavernosum smooth muscle tone associated with partial bladder outlet obstruction is mediated via Rho-kinase. Am J Physiol Regul Integr Comp Physiol. 2005; 289:R1124–30.

11). Khan MA, Dashwood MR, Thompson CS, Auld J, Morgan RJ, Mikhailidis DP. Down-regulation of endothelin-B receptor sites in cavernosal tissue of a rabbit model of partial bladder outlet obstruction: potential clinical relevance. World J Urol. 1999; 17.

12). Kohan DE. Endothlins in the normal and diseased kidney. Am J Kidney Dis. 1997; 29:2–26.

13). Lin HY, Kaji EH, Winkel GK, Ives HE, Lodish HF. Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Proc Natl Acad Sci USA. 1991; 88:3185–9.

14). Warner TD, De Nucci G, Vane JR. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol. 1989; 159:325–6.

15). Simonson MS, Dunn MJ. Cellular signaling by pep-tides of the endothelin gene family. FASEB J. 1990; 4:2989–3000.

16). Sullivan ME, Dashwood MR, Thompson CS, Muddle JR, Mikhailidis DP, Morgan RJ. Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction. J Urol. 1997; 158:1966–72.

17). Sullivan ME, Dashwood MR, Thompson CS, Mikhailidis DP, Morgan RJ. Down-regulation of endothelin-B receptor sites in cavernosal tissue of hy-percholesterolaemic rabbits. Br J Urol. 1998; 81:128–34.

18). Goettsch W, Lattmann T, Amann K, Szibor M, Morawietz H, Munter K, et al. Increased expression of endothelin-1 and inducible nitric oxide synthase isoform II in aging arteries in vivo: implications for atherosclerosis. Biochem Biophys Res Commun. 2001; 280:908–13.

19). Park BK, Oh GS, Park NC. Age-related changes of nitric oxide synthase isoforms and endothelin-1 in rat corpus cavernosum. Korean J Urol. 2005; 46:1213–20.

20). Lin WY, Mannikarottu A, Chichester P, Guven A, Johnson A, Neuman P, et al. Changes in the smooth muscle of the corpora cavernosum related to reversal of partial bladder outlet obstruction in rabbits. J Androl. 2008; 29:164–71.