Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Br J Pharmacol. 2011 Jul;163(6):1276-88. doi: 10.1111/j.1476-5381.2011.01311.x.
Diabetic cystopathy is one of the most common and incapacitating complications of diabetes mellitus. This study aimed to evaluate the functional, structural and molecular alterations of detrusor smooth muscle (DSM) in streptozotocin-induced diabetic mice, focusing on the contribution of Ca(2+) influx through L-type voltage-operated Ca(2+) channels (L-VOCC).
Male C57BL/6 mice were injected with streptozotocin (125 mg·kg(-1) ). Four weeks later, contractile responses to carbachol, α,β-methylene ATP, KCl, extracellular Ca(2+) and electrical-field stimulation were measured in urothelium-intact DSM strips. Cystometry and histomorphometry were performed, and mRNA expression for muscarinic M(2) /M(3) receptors, purine P2X1 receptors and L-VOCC in the bladder was determined.
Diabetic mice exhibited higher bladder capacity, frequency, non-void contractions and post-void pressure. Increased bladder weight, wall thickness, bladder volume and neural tissue were observed in diabetic bladders. Carbachol, α,β-methylene ATP, KCl, extracellular Ca(2+) and electrical-field stimulation all produced greater DSM contractions in diabetic mice. The L-VOCC blocker nifedipine almost completely reversed the enhanced DSM contractions in bladders from diabetic animals. The Rho-kinase inhibitor Y27632 had no effect on the enhanced carbachol contractions in the diabetic group. Expression of mRNA for muscarinic M(3) receptors and L-VOCC were greater in the bladders of diabetic mice, whereas levels of M(2) and P2X1 receptors remained unchanged.
Diabetic mice exhibit features of urinary bladder dysfunction, as characterized by overactive DSM and decreased voiding efficiency. Functional and molecular data suggest that overactive DSM in diabetes is the result of enhanced extracellular Ca(2+) influx through L-VOCC.
糖尿病性膀胱病是糖尿病最常见和使人丧失能力的并发症之一。本研究旨在评估链脲佐菌素诱导的糖尿病小鼠逼尿肌平滑肌（DSM）的功能、结构和分子改变，重点关注通过 L 型电压门控钙通道（L-VOCC）的钙内流的贡献。
雄性 C57BL/6 小鼠注射链脲佐菌素（125mg·kg(-1)）。4 周后，在完整尿路上皮的 DSM 条带中测量乙酰胆碱、α，β-亚甲基 ATP、KCl、细胞外 Ca(2+)和电场刺激引起的收缩反应。进行尿动力学和组织形态计量学，并确定膀胱中毒蕈碱 M(2)/M(3)受体、嘌呤 P2X1 受体和 L-VOCC 的 mRNA 表达。
糖尿病小鼠表现出更高的膀胱容量、频率、非排空收缩和排空后压力。糖尿病膀胱中观察到膀胱重量、壁厚度、膀胱容量和神经组织增加。在糖尿病小鼠中，乙酰胆碱、α，β-亚甲基 ATP、KCl、细胞外 Ca(2+)和电场刺激均引起 DSM 收缩增强。L-VOCC 阻滞剂硝苯地平几乎完全逆转了糖尿病动物膀胱中增强的 DSM 收缩。Rho-激酶抑制剂 Y27632 对糖尿病组中增强的乙酰胆碱收缩没有影响。糖尿病小鼠膀胱中 muscarinic M(3)受体和 L-VOCC 的 mRNA 表达增加，而 M(2)和 P2X1 受体的水平保持不变。
糖尿病小鼠表现出膀胱功能障碍的特征，表现为 DSM 过度活跃和排尿效率降低。功能和分子数据表明，糖尿病中 DSM 的过度活跃是由于细胞外 Ca(2+)通过 L-VOCC 增强内流所致。
