Serkan KARAİSMAİLOĞLU, Zeynep Dicle BALKANCI, Bilge PEHLİVANOĞLU, Sibel BAYRAK, İsmail KARABULUT, Ayşen ERDEM

The effect of hypercholesterolemia on the contractions of detrusor strips in response to neural stimulation in rats

To investigate the effect of hypercholesterolemia on in vitro contractions of the detrusor smooth muscle stimulated by an electrical field in rats and the relative contributions of cholinergic and noncholinergic neurotransmission. Materials and methods: Sprague-Dawley rats were fed with standard diet (NC group) or with 4% cholesterol diet (HC group). After 4 weeks, the urinary bladder was excised under anesthesia and 4 detrusor strips were prepared. Blood samples were collected for serum lipid profile, and aortic arches were dissected for histopathological examination. In vitro contractile function of the detrusor smooth muscle was evaluated with: 1) electrical field stimulation (EFS) only, 2) EFS in the presence of muscarinic antagonist atropine (10-6 M), and 3) EFS in the presence of atropine and P2X antagonist phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (10-4 M) or P2X agonist a,b-methylene-adenosine-5'-triphosphate (10-5 M). Results: Plasma cholesterol was elevated in the HC group (P < 0.05); there was no sign of atherosclerosis. Although EFS-induced contractions were higher in the HC group, the difference was not significant. Cholinergic or purinergic antagonists decreased contractile response by desensitization with the purinergic agonist. The contribution of cholinergic and purinergic components were also similar in both groups. Conclusion: The contribution of cholinergic and noncholinergic mechanisms of neurotransmission seems to be independent of the high cholesterol content of the diet and the plasma cholesterol level in rat detrusor muscle.

Anahtar Kelimeler:

Key words: Cholesterol, cholinergic, urinary bladder, electrical field stimulation, purinergic

The effect of hypercholesterolemia on the contractions of detrusor strips in response to neural stimulation in rats

Keywords:

Key words: Cholesterol, cholinergic, urinary bladder, electrical field stimulation, purinergic,

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Andersson KE, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 2004; 84: 935–86.
Somogyi GT, Zernova GV, Yoshiyama M, Yamamoto T, de Groat WC. Frequency dependence of muscarinic facilitation of transmitter release in urinary bladder strips from neurally intact or chronic spinal cord transected rats. Br J Pharmacol 1998; 125: 241–6. 3. Carpenter FG. Atropine resistance and muscarinic receptors in the rat urinary bladder. Br J Pharmacol 1977; 59: 43–9.
Theobald RJ Jr. Purinergic and cholinergic components of bladder contractility and flow. Life Sci 1995; 56: 445–54.
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232: 34–47.
Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell 1992; 68: 673–82.
Cohen AW, Hnasko R, Schubert W, Lisanti MP. Role of caveolae and caveolins in health and disease. Physiol Rev 2004; 84: 1341–79.
Levitan I, Fang Y, Rosenhouse-Dantsker A, Romanenko V. Cholesterol and ion channels. Subcell Biochem 2010; 51: 509– 49.
Lai HH, Bone TB, Yang G, Smith CP, Kiss S, Thompson TC et al. Loss of caveolin-1 expression is associated with disruption of muscarinic cholinergic activities in the urinary bladder. Neurochem Int 2004; 45: 1185–93.
Azadzoi KM, Tarcan T, Kozlowski R, Krane RJ, Siroky MB. Overactivity and structural changes in the chronically ischemic bladder. J Urol 1999; 162: 1768–78.
Rahman NU, Phonsombat S, Bochinski D, Carrion RE, Nunes L, Lue TF. An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat. BJU Int 2007; 100: 658–63.
Son H, Lee SL, Park WH, Park K, Park S, Kang MS et al. New unstable bladder model in hypercholesterolemia rats. Urology 2007; 69: 186–90.
Huang YC, Shindel AW, Ning H, Lin G, Harraz AM, Wang G et al. Adipose derived stem cells ameliorate hyperlipidemia associated detrusor overactivity in a rat model. J Urol 2010; 183: 1232–40.
Nomiya M, Yamaguchi O, Andersson KE, Sagawa K, Aikawa K, Shishido K et al. The effect of atherosclerosis-induced chronic bladder ischemia on bladder function in the rat. Neurourol Urodyn 2012; 31: 195–200.
Longhurst PA, Uvelius B. Pharmacological techniques for the in vitro study of the urinary bladder. J Pharmacol Toxicol Methods 2001; 45: 91–108.
Palea S, Artibani W, Ostardo E, Trist DG, Pietra C. Evidence for purinergic neurotransmission in human urinary bladder affected by interstitial cystitis. J Urol 1993; 150: 2007–12.
Liu G, Daneshgari F. Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes. Am J Physiol Renal Physiol 2005; 288: 1220–6.
Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev 2004, 56: 581–631.
Hall SA, Chiu GR, Link CL, Steers WD, Kupelian V, McKinlay JB. Are statin medications associated with lower urinary tract symptoms in men and women? Results from the Boston Area Community Health (BACH) Survey. Ann Epidemiol 2011, 21:149–155.
Lee WC, Chao WT, Yang VC. Effects of high-cholesterol diet on the interendothelial clefts and the associated junctional complexes in rat aorta. Atherosclerosis 2001; 155: 307–12.
Balkancı ZD, Pehlivanoğlu B, Bayrak S, Karabulut İ, Karaismailoğlu S, Erdem A. The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels. Naunyn- Schmiedeberg’s Arch Pharmacol 2012; 385: 1141–8.
Kennedy C, Tasker PN, Gallacher G, Westfall TD. Identification of atropine- and P2X1 receptor antagonist-resistant, neurogenic contractions of the urinary bladder. J Neurosci 2007; 27: 845–51.
Aronsson P, Andersson M, Ericsson T, Giglio D. Assessment and characterization of purinergic contractions and relaxations in the rat urinary bladder. Basic Clin Pharmacol Toxicol 2009; 107: 603–13.
Cai GJ, Miao CY, Xie HH, Lu HH, Su DF. Arterial baroreflex dysfunction promotes atherosclerosis in rats. Atherosclerosis 2005; 183: 41–7.
Lluel P, Barras M, Palea S. Cholinergic and purinergic contribution to the micturition reflex in conscious rats with long-term bladder outlet obstruction. Neurourol Urodyn 2002; 21: 142–53.
Banks FC, Knight GE, Calvert RC, Morgan RJ, Burnstock G. Alterations in purinergic and cholinergic components of contractile responses of isolated detrusor contraction in a rat model of partial bladder outlet obstruction. BJU Int 2006; 97: 372–8.
Sjögren C, Andersson KE, Husted S, Mattiasson A, Moller- Madsen B. Atropine resistance of transmurally stimulated isolated human bladder muscle. J Urol 1982; 128: 1368–71.
Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A. Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urol 2004; 63: 17–23.
Khattab MM, Al-Hrasen MN, El-Hadiyah TM. Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in the rat: role of A1- and P2X-purinoceptors and nitric oxide. Auton Autacoid Pharmacol 2007; 27: 55–62.
Yoshida A, Kageyama A, Fujino T, Nozawa Y, Yamada S. Loss of muscarinic and purinergic receptors in urinary bladder of rats with hydrochloric acid-induced cystitis. Urology 2010; 76: 1017.e7–1017.e12.
Hashimoto M, Kokubun S. Contribution of P2-purinoceptors to neurogenic contraction of rat urinary bladder smooth muscle. Br J Pharmacol 1995; 115: 636–40.
Rouissi N, Nantel F, Drapeau G, Rhaleb NE, Dion S, Regoli D. Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, bradykinin and angiotensin in guinea pig, hamster and rat urinary bladders. Pharmacology 1990; 40: 196–204.
Meini S, Maggi CA. Evidence for a capsaicin-sensitive, tachykinin-mediated, component in the NANC contraction of the rat urinary bladder to nerve stimulation. Br J Pharmacol 1994; 112: 1123–31.
Azadzoi KM, Shinde VM, Tarcan T, Kozlowski R, Siroky MB. Increased leukotriene and prostaglandin release, and overactivity in the chronically ischemic bladder. J Urol 2003; 169: 1885–91.