Ratlarda Yaşlanmanın Mesane Fonksiyonları Üzerinde Oluşturduğu Değişikliklerin İncelenmesi

Amaç: Alt üriner sistem semptomları (AÜSS) sadece iyi huylu prostat hiperplazisine (BPH) bağlı olmayıp, mesanede yapısal veya fonksiyonel değişikliklere neden olabilecek herhangi bir durum AÜSS'nin gelişmesiyle ilişkili olabilir. Bununla birlikte, AÜSS'lere yol açan kesin mekanizmalar henüz net bir şekilde tanımlanmamıştır. Bu deneysel çalışmada yaşlanmanın organ banyosu ortamında mesane fonksiyonları üzerinde oluşturduğu değişikliklerin incelenmesi amaçlandı. Gereç ve Yöntemler: Çalışmada kullanılan Wistar cinsi sıçanlar 10 adet yaşlı (24 aylık) ve 10 adet genç (6 aylık) olmak üzere iki gruba ayrıldı. Detrüsör şeritleri, içerisinde Krebs- Heinseleit çözeltisi bulunan organ banyosuna asıldı. Kontraksiyon için asetilkolin ve KCl kullanılırken, aynı ajanların L-NAME (Nω-Nitro-L-argininemethylester) varlığında verdikleri yanıtlar ölçüldü. Gevşeme için asetilkolin ve KCl ile kasılmış dokularda fenilefrin ve sodyum nitroprussid yanıtları ölçüldü. Elde edilen veriler student’s t testi kullanılarak istatistiksel olarak karşılaştırıldı. Bulgular: Genç ve yaşlı sıçan detrusörünün kasılma yanıtları karşılaştırıldığında, asetilkolinin yüksek konsantrasyonlarında gençlerde kasılma gücü yaşlı gruba göre belirgin yüksek bulundu. Yine L-NAME varlığında asetilkoline alınan yanıt aynı şekilde anlamlı olarak yüksek bulunurken, her iki grup arasında KCl ve L-NAME varlığında KCl’ye alınan yanıtlarda anlamlı farklılık saptanmadı. Gevşeme yanıtlarına bakıldığında ise asetilkolinle kasılmış yaşlı sıçan mesanelerinin, gençlere göre fenilefrine ve sodyum nitroprusside düşük dozlarda anlamlı gevşeme yanıtı verdiği görüldü. KCl ile kasılmış dokularda ise yaşlı sıçanların sodyum nitroprussid için düşük, fenilefrin için ise yüksek konsantrasyonlarda anlamlı gevşeme yanıtı gösterdiği görüldü. Sonuç: Organ banyosu kullanılarak yapılan bu deneysel çalışmada, genç ve yaşlı rat mesanelerinde kontraktil ve gevşetici özellikte aynı ajanlara karşı farklı yanıtların alınması, yaşlanmayla mesanenin reseptör karakteristiklerinde değişiklik oluştuğunu düşündürmektedir. Dolayısıyla bu gözlem, yaşlanmanın mesane fonksiyonlarını etkileyerek AÜSS’ye neden olabileceği görüşünü desteklemektedir.

Anahtar Kelimeler:

Yaşlanma, mesane, rat, organ banyosu

Evaluation of Alterations in Bladder Functions Associated With Aging in Rats

Objective: It is clearly know that lower urinary tract symptoms (LUTS) are not solely associated with benign prostatic hyperplasia. Any process that can cause structural or functional changes in the bladder might also be related with the development of LUTS. Nevertheless, the exact mechanisms causing LUTS have not clearly been defined yet. The aim of this experimental study was to investigate the impact of aging on detrusor functions using organ bath. Material and Methods: Rats were divided into two groups as young and old. The first group consited of 10 rats with 6 monts of age, while the second group contained 10 rats with 24 months of age. The isolated detrusor strips were placed in the organ bath containing Krebs -Heinseleit solution. Ach (Acetylcholine) and KCl were utilized to study contraction. The response to same agents were obtained with the addition of L-NAME (Nω-Nitro-L-arginine methyl ester). Relaxation function was compared between these groups by using phenilefrine and SNP (Sodium nitropruccide). Student’s t test was used to assess the statistical significance. Results: The contraction response to Ach with high concentrations was significantly powerful in young rats with compare to old rats. A similar significant response was observed in young rats when L-NAME was added to Ach. However, no significant difference was seen when KCl was applied. On the other hand, the old rats showed a significant relaxation response when low concentrations of phenilefrine and SNP were utilized in muscles that had been concracted by Ach. Moreover, when the muscles had been concracted by KCl, a significantly higher relaxation was noticed by using low concentrations of SNP and high concentrations of phenilefrine in old rats with compare to young rats. Couclusion: In this experimental study of aging bladder, a remarkable difference in bladder functions was observed between young and old rats in terms of responding various agents by using organ bath. This finding suggets a possible alteration in receptor properties of the bladder aging. Therefore, it can be postulated that aging may cause alterations in bladder functions which in turn may be associated with development of LUTS.

Keywords:

Aging, bladder, rat, organ bath,

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1. Garrawy WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet 1991; 338: 469-71
2. Chapple CR. The total approach in lower urinary tract symptoms. Benign prostatic hyperplasia (LUTS-BPH) management: Introduction and conclusion. Euro Urol 2003; 2 (spp): 1-5.
3. Lee AS, Garrawy WM, Simpson RJ, Fisher W, King D. The natürel history of untreated lower urinary tracts ymptom in middle age and elderly men over a period of five years. Euro Urol. 1998; 34: 325-32.
4. Poulsen AL, Schou J, Puggaard L, Torp – Pedersen S, Nordling J. Prostatic enlargement, semptomatology and pressure flow evaluation: interrelations in patients with symptomatic BPH. Scand J Urol Nephrol. 1994; 157: 67-74.
5. Holtgrewe HL. Transurethral prostatectomy. Urol Clin North Am 1995;22: 357-63.
6. Madersbacher S, Phyca A, Schatzi G et al. The aging lower urinary tract: a comparative urodynamic study of men and women. Urology 1998;51: 206-11.
7. Cellek S, Cameron NE, Cotter MA, Fry CH, Ilo D. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH-LUTS. Nat Rev Urol. 2014;11(4):231-41.
8. Chancoller MB, Yoshimura N. Physiology and pharmacology of the bladder and urethra. Campbell’sUrology (Walsh PC, Retik AB, Vaughan ED, Wein AJ). Eightedition. Phiadelphia, Saunders. 2002; Vol 2: 831-86.
9. Kondo S, Morita T, Tashima Y. Muscarinic cholinergic receptor subtypes in human detrusor muscle studied by labeled and nonlabeled prenzepine, AFDX-116 and DAMP. Urol Int. 1995; 54: 150-158.
10. Harris DR, Marsh KA, Birmingham AT. Expression of muscarinic M3 receptors coupled to inositol phospholipid hidrolisis in human detrusor muscle cells. J Urol. 1995; 154: 150-158.
11. Park YC, Tomiyama Y, Hayakawa K, Akahane M, Ajisawa Y, Miyatke R. Existence of a β3 adreno receptor and it functional role in the human ureter. J Urol. 2000;164: 1364-70.
12. Lepor H, Gup D, Shapiro E, Baumann M. Muscarinic cholinergic receptors in the normal and neurogenic humanbladder. J Urol. 1989; 142:869-74.
13. McGurray G, Dass N, Ho KMT, Brading AF. Purinergicm echanisms in primate urinary bladder. Br J Urol. 1997; 80: 182-88.
14. Canda A.E, Cross C.R, Chapple C.R. Pharmacology of the Lower Urinary Tract and Management of Overactive Bladder. J Turkish-GermanGynecolAssoc, 2006:7;146-57.
15. Anderson KE, Persson K. Nitricoxide synthase and the lower urinary tract: Possible implications for physiology and pathophysiology. Scand J Urol Nephrol. 1995;175: 45-51.
16. Hennenberg M, Stief CG, Gratzke C. Pharmacology of the lower urinary tract. Indian J Urol. 2014 Apr-Jun; 30(2): 181–188.
17. Remzi D, Tekgül S. Alt üriner sistemin yaşlanma ve infravezikal obstrüksiyona cevabı. Özen HA(edt): Benign prostat hiperplazisi. Hekimler yayın birliği, Ankara,1996; s:49-51.
18. Andersson KE, Boedtkjer DB, Forman A. The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction. TherAdv Urol. 2017; 9(1): 11–27.
19. Lewin R, Malkowicz B, Wein AJ. Recovery from short term obstruction of the rabbit urinary bladder. J Urol 1985;134: 134-9.
20. Mostin JL, Karim OM, Koeveringe V. Theguinapig as a model of gradual urethral obstruction. J Urol. 1991;148: 854-9.
21. Wein AJ. Assessing treatment result in benign prostatic hiperplasia. Urol Clin North Am. 1995;22: 345-50.
22. Couillard DR, Webster GD. Detrusorinstability. Urol Clin North Am. 1995;22: 593-98.
23. Artibani W. Diagnosis and significance of idiopathic overactive bladder. Urology. 1997; 50: 25-31.
24. Azadzoi KM, Tarcan T, Kozlowsky R, Krani JR, Siroky MB. Over activity and structural changes in the chronically ischemic bladder. J Urol. 1999;162: 1768-78.
25. Pinggera G, Mitterberger M, Pallwein L et al. Alpha-Blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms. BJU Int. 2008;101: 319–324.
26. Saito M, Ohmura M, Kndo A. Effects of aging on blood flow to the bladder and bladder function. Urol Int. 1999;62: 93-98.
27. Nishimoto T, Latifpour J, Wheeler MA, Yoshida M, Weiss RM. Aged dependent alterations in β adrenergic responsiveness of rat detrusor smooth muscle. J Urol. 1995;153: 1701-05.
28. Steers WD. Physiology and phamocology of the bladder and urethra. Campbell’sUrology (Walsh PC, Retik AB, Vaughan ED, Wein AJ). Seven edition. Saunderscompany, Phiadelphia. 1997; 870-915.
29. Zar MA, Irawani MM, Luheshi GN. Effect of nifedepine on the concractile responses of the isolated rat bladder. J Urol. 1990;143: 835-39.
30. Luheshi GN, Zar MA. Purinoceptor desensitization impairs but dose not abolish the noncholinergic motor transmission in rat isolated urinary bladder. Eur J Pharmacol. 1990;185: 203-08.
31. Ozawa H, Chancellor MB, Jung SY. Effect of intra vesical nitricoxide therapy on cyclophosphamide induced cytitis. J Urol. 1999;162: 2211-16.
32. Yoshida M, Homma Y, Inadome A et al. Age related changes in cholinergic and purinergic neurotransmission in human izolated bladder smooth muscle. Exp Gerontology. 2001;36: 99-109.
33. Saito M, Kondo A, Gotoh M. Age related changes in the response of the rat urinary bladder to neurotransmitters. NeurourolUrodyn. 1993; 12:191-197.
34. Lin ATL, Yang CH, Chang LS, Chen MT. Age related changes on the adrenergic contractile response in the urinary bladder and the prostate. Neurourol Urodyn. 1992;11: 304-9.
35. Kamei J, Ito H, Aizawa N et al. Age-related changes in function and gene expression of the male and female Mouse bladder. Sci Rep. 2018 Feb 1;8(1):2089-98.