Effect of Nebivolol on the Isolated Rat Bladder Strips Precontracted with Carbachol or Potassium Chloride

Year 2020, Volume: 10 Issue: 3, 316 - 319, 29.09.2020

Hande Ozge Altunkaynak-camca

https://doi.org/10.33808/clinexphealthsci.731484

Abstract

Amaç: Nebivololün vazorelaksan etkisine aracılık ettiği öne sürülen mekanizmalar arasında beta-2 ve/veya beta-3 adrenerjik reseptörler üzerindeki agonistik aktivitesi yer alır. Bu reseptörler, aynı zamanda mesanenin gevşemesiyle de ilişkilidir. Bu çalışmanın amacı, kolinerjik bir uyaran karbakol veya non-kolinerjik bir uyaran potasyum klorür (KCl) kullanılarak kasılmış izole sıçan mesane şeritlerinde nebivololün relaksan etkisini araştırmaktı.
Yöntem: İzole edilmiş mesane şeritleri organ banyosuna asıldı ve nebivolol (0.0001-100 µM) kümülatif olarak eklenmeden önce KCl (40 mM) veya karbakol (1 µM) ile mesane şeritleri kasıldı. Bu yanıtta beta-adrenerjik reseptörlerin rolünü araştırmak için bazı mesane şeritleri propranolol (1 µM) ile 30 dakika boyunca inkübe edildi. Karşılaştırmalarda Student’s t-testi kullanıldı. p<0.05 istatistiksel olarak anlamlı kabul edildi.
Bulgular: Nebivolol KCl veya karbakol ile kasılmış mesane şeritlerinde konsantrasyon-bağımlı gevşeme yanıtına yol açtı. Propranolol varlığında, karbakolle kasılmış izole sıçan mesane şeritlerindeki nebivololün relaksan etkisi anlamlı olarak (p<0.05) inhibe edilmesine karşın KCl ile kasılmış mesane şeritlerinde nebivololün relaksan etkisi propranolol ile inhibe edilemedi. Karbakolle kasılan mesane şeritlerinde nebivolole verilen maksimum yanıt KCl ile kasılanlarla kıyasla anlamlı olarak daha yüksek bulundu (p<0.05).
Sonuç: Bu çalışmanın bulguları, karbakolle kasılmış izole mesane şeritlerinde nebivololün relaksan etkisinde beta-adrenerjik reseptörlerin rolü olduğuna işaret etmektedir.

Keywords

Nebivolol, relaksasyon, karbakol, potasyum klorür, mesane

Effect of Nebivolol on the Isolated Rat Bladder Strips Precontracted with Carbachol or Potassium Chloride

Abstract

Objective: One of the proposed mechanism mediates the vasorelaxant effect of nebivolol is based on its agonistic activity on beta-2 and/or beta-3 adrenergic receptors. These receptors are also involved in the relaxation of urinary bladder. The aim of this study was to explore that the ability of nebivolol to induce relaxation of the isolated rat bladder strip precontracted with cholinergic stimuli using with carbachol or non-cholinergic stimuli using with potassium chloride (KCl).
Methods: The isolated bladder strips were mounted in organ bath and contracted by KCl (40 mM) or carbachol(1 µM) before the cumulative addition of nebivolol (0.0001-100 µM). To investigate the role of beta-adrenergic receptors in the nebivolol-induced relaxant response, some bladder strips were incubated with propranolol (1 µM) for 30 min. Statistical significance was tested by Student’s t-test. p<0.05 was considered to be statistically significant.
Results: Nebivolol elicited concentration-dependent relaxant response in the bladder strips precontracted with KCl or carbachol. Although the relaxant response to nebivolol in the bladder strips precontracted with carbachol was significantly inhibited by propranolol(p<0.05), the nebivolol-induced relaxation was failed to be inhibited by propranolol in the bladder strips precontracted with KCl. The maximum relaxation in response to nebivolol was found to be significantly higher in the bladder strips precontracted with carbachol compared to that of KCl (p<0.05).
Conclusion: The findings of the present study indicate that beta-adrenergic receptors play role in the relaxant response of nebivolol in the isolated rat bladder strip precontracted with carbachol.

Keywords

Nebivolol, relaxation, carbachol, potassium chloride, bladder

References

• 1. Olawi N, Krüger M, Grimm D, Infanger M, Wehland M. Nebivolol in the treatment of arterial hypertension. Basic & Clinical Pharmacology & Toxicology. 2019; 125(3): 189-201. 2. Cicero AFG, Kuwabara M, Borghi C. A critical review of nebivolol and its fixed-dose combinations in the treatment of hypertension. Drugs. 2018; 78(17): 1783-1790. 3. Broeders MA, Doevendans PA, Bekkers BC, et al. Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide production. Circulation. 2000; 102(6): 677-684. 4. de Groot AA, Mathy MJ, van Zwieten PA, Peters SL. Involvement of the beta3 adrenoceptor in nebivolol-induced vasorelaxation in the rat aorta. Journal of Cardiovascular Pharmacology. 2003; 42(2): 232-236. 5. Aizawa N, Homma Y, IgawaY. Effects of mirabegron, a novel β3‐adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin. European urology. 2012; 62 (6): 1165‐1173. 6. Igawa Y, Schneider T, Yamazaki Y, et al. Functional investigation of β‐adrenoceptors in human isolated detrusor focusing on the novel selective β3‐adrenoceptor agonist KUC‐7322. Naunyn-Schmiedeberg's archives of pharmacology. 2012; 385 (8): 759‐767. 7. Propping S, Newe M, Lorenz K, Wirth MP, Ravens U. β-Adrenoceptor-mediated relaxation of carbachol-pre-contracted mouse detrusor. Urologia internationalis, 2015; 95 (1): 92–98. 8. Oshita M, Hiraoka Y, Watanabe,Y. Characterization of beta-adrenoceptors in urinary bladder: comparison between rat and rabbit. British journal of pharmacology. 1997; 122(8): 1720-1724. 9. Yamazaki Y, Takeda H, Akahane M, Igawa Y, Nishizawa O, Ajisawa Y. Species differences in the distribution of beta-adrenoceptor subtypes in bladder smooth muscle. British journal of pharmacology. 1998; 124(3): 593-599. 10. Visser AJ, van Mastrigt R. The role of intracellular and extracellular calcium in mechanical and intracellular electrical activity of human urinary bladder smooth muscle. Urological research. 2000; 28(4): 260-268. 11. Obara K, Suzuki S, Shibata H, et al. Noradrenaline-induced relaxation of urinary bladder smooth muscle is primarily triggered through the β3-adrenoceptor in rats. Biological and pharmaceutical bulletin. 2019; 42(5): 736–743. 12. Michel MC, Sand C. Effect of pre-contraction on β-adrenoceptor-mediated relaxation of rat urinary bladder. World journal of urology. 2009; 27(6): 711-715. 13. Levin RM, Whitbeck C, Sourial MW, Tadrous M, Millington WR. Effects of dextromethorphan on in vitro contractile responses of mouse and rat urinary bladders. Neurourology and urodynamics. 2006; 25(7): 802-807. 14. Tan Z, Xiao Z, Wei J, et al. Nebivolol suppresses cardiac ryanodine receptor-mediated spontaneous Ca2+ release and catecholaminergic polymorphic ventricular tachycardia. Biochemical journal. 2016; 473(22): 4159-4172. 15. Cseplo P, Vamos Z, Ivic I, Torok O, Toth A, Koller A. The beta-1-receptor blocker nebivolol elicits dilation of cerebral arteries by reducing smooth muscle [Ca2+]i. PLoS One. 2016; 11(10): e0164010. 16. Uchida H, Shishido K, Nomiya M, Yamaguchi O. Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors. European Journal of Pharmacology. 2005; 518(2-3):195-202. 17. Masunaga K, Chapple CR, McKay NG, Yoshida M, Sellers DJ. The β3-adrenoceptor mediates the inhibitory effects of β-adrenoceptor agonists via the urothelium in pig bladder dome. Neurourology and urodynamics. 2010; 29(7): 1320-1325. 18. Frazier EP, Michel-Reher MB, van Loenen P, et al. Lack of evidence that nebivolol is a β₃-adrenoceptor agonist. European Journal of Pharmacology. 2011; 654(1): 86-91.