Bayrak Sibel, Balkanci Zeynep Dicle, Pehlivanoğlu Bilge, Karabulut İsmail, Karaismailoğlu Serkan, Erdem Ayşen
Department of Physiology, Faculty of Medicine, Hacettepe University, 39, 06100, Sihhiye, Ankara, Turkey,
Naunyn Schmiedebergs Arch Pharmacol. 2015 Jul;388(7):761-71. doi: 10.1007/s00210-014-1060-7. Epub 2014 Oct 26.
To evaluate the effects of hypercholesterolemia on the relaxation function of the urinary bladder, we examined the physiological mechanisms involved in the isoproterenol-induced relaxation in isolated detrusor strips in vitro and voiding behavior in vivo in rats. Adult male Sprague-Dawley rats were fed standard (control, N = 16) or 4 % cholesterol diet (hypercholesterolemia, N = 17) for 4 weeks. Concentration-response curves for isoproterenol-induced relaxations in carbachol-precontracted detrusor muscle strips were recorded. The contributions of β2- and β3-adrenoceptors and ATP-dependent and Ca(2+)-dependent potassium channels to the relaxation response were investigated by using selective adrenergic agonists salbutamol and BRL 37344 and specific potassium channel inhibitors glibenclamide and charybdotoxin, respectively. Cystometrography was performed to assess bladder function. Hypercholesterolemic rats had higher serum cholesterol and low- and high-density lipoprotein levels than the controls with no sign of atherosclerosis. Isoproterenol-induced relaxation was significantly enhanced in the hypercholesterolemia group. Preincubation with the M2 receptor antagonist attenuated the relaxation response in both groups. The relaxation responses to isoproterenol and salbutamol were similar in both groups, while BRL 37344 appeared to produce a greater relaxant effect in the hypercholesterolemic rats. Also, the inhibitory effects of potassium channel inhibitors on relaxation responses were comparable among the groups. The cystometric findings revealed that threshold and basal pressure values were higher in the hypercholesterolemia group compared with controls. We showed that hypercholesterolemia leads to greater relaxation responses to isoproterenol, appears to impair the braking function of M2 cholinergic receptors on adrenoceptor-induced relaxations in the isolated detrusor muscle, and affects the voiding function in rats.
为评估高胆固醇血症对膀胱舒张功能的影响，我们研究了体外分离逼尿肌条中异丙肾上腺素诱导舒张所涉及的生理机制以及大鼠体内的排尿行为。成年雄性Sprague-Dawley大鼠分别喂食标准饮食（对照组，N = 16）或4%胆固醇饮食（高胆固醇血症组，N = 17），持续4周。记录卡巴胆碱预收缩的逼尿肌条中异丙肾上腺素诱导舒张的浓度-反应曲线。分别使用选择性肾上腺素能激动剂沙丁胺醇和BRL 37344以及特异性钾通道抑制剂格列本脲和大蝎毒素，研究β2和β3肾上腺素能受体以及ATP依赖性和Ca(2+)依赖性钾通道对舒张反应的作用。进行膀胱压力容积测定以评估膀胱功能。高胆固醇血症大鼠的血清胆固醇、低密度和高密度脂蛋白水平高于对照组，且无动脉粥样硬化迹象。高胆固醇血症组中异丙肾上腺素诱导的舒张明显增强。用M2受体拮抗剂预孵育可减弱两组的舒张反应。两组对异丙肾上腺素和沙丁胺醇的舒张反应相似，而BRL 37344在高胆固醇血症大鼠中似乎产生更大的舒张作用。此外，钾通道抑制剂对舒张反应的抑制作用在各组之间相当。膀胱压力容积测定结果显示，与对照组相比，高胆固醇血症组的阈值和基础压力值更高。我们发现，高胆固醇血症导致对异丙肾上腺素的舒张反应增强，似乎损害了M2胆碱能受体对离体逼尿肌中肾上腺素能受体诱导舒张的制动功能，并影响大鼠的排尿功能。
