Gómez-Pinilla Pedro J, Pozo Maria J, Camello Pedro J
Faculty of Veterinary Sciences, Department of Physiology, University of Extremadura, Cáceres, Spain.
Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R793-803. doi: 10.1152/ajpregu.00034.2007. Epub 2007 May 23.
The incidence of urinary bladder disturbances increases with age, and free radical accumulation has been proposed as a causal factor. Here we investigated the association between changes in bladder neuromuscular function and oxidative stress in aging and the possible benefits of melatonin treatment. Neuromuscular function was assessed by electrical field stimulation (EFS) of isolated guinea pig detrusor strips from adult and aged female guinea pigs. A group of adult and aged animals were treated with 2.5 mg x kg(-1) x day(-1) melatonin for 28 days. Neurotransmitter blockers were used to dissect pharmacologically the EFS-elicited contractile response. EFS induced a neurogenic and frequency-dependent contraction that was impaired by aging. This impairment is in part related to a decrease in detrusor myogenic contractility. Age also decreased the sensitivity of the contraction to pharmacological blockade of purinergic and sensitive fibers but increased the effect of blockade of nitrergic and adrenergic nerves. The density of cholinergic and nitrergic nerves remained unaltered, but aging modified afferent fibers. These changes were associated with an increased level of markers for oxidative stress. Melatonin treatment normalized oxidative levels and counteracted the aging-associated changes in bladder neuromuscular function. In conclusion, these results show that aging modifies neurogenic contraction and the functional profile of the urinary bladder plexus and simultaneously increases the oxidative damage to the organ. Melatonin reduces oxidative stress and improves the age-induced changes in bladder neuromuscular function, which could be of importance in reducing the impact of age-related bladder disorders.
膀胱功能紊乱的发生率随年龄增长而增加，自由基积累被认为是一个致病因素。在此，我们研究了衰老过程中膀胱神经肌肉功能变化与氧化应激之间的关联，以及褪黑素治疗的潜在益处。通过对成年和老年雌性豚鼠分离的逼尿肌条进行电场刺激（EFS）来评估神经肌肉功能。一组成年和老年动物接受2.5 mg x kg(-1) x day(-1)的褪黑素治疗，持续28天。使用神经递质阻滞剂从药理学角度剖析EFS引发的收缩反应。EFS诱导了一种神经源性且频率依赖性的收缩，衰老会损害这种收缩。这种损害部分与逼尿肌肌源性收缩力下降有关。年龄还降低了收缩对嘌呤能和敏感纤维药理学阻断的敏感性，但增加了对一氧化氮能和肾上腺素能神经阻断的效果。胆碱能和一氧化氮能神经的密度保持不变，但衰老改变了传入纤维。这些变化与氧化应激标志物水平的升高有关。褪黑素治疗使氧化水平正常化，并抵消了衰老相关的膀胱神经肌肉功能变化。总之，这些结果表明，衰老会改变神经源性收缩和膀胱神经丛的功能特征，同时增加对器官的氧化损伤。褪黑素可降低氧化应激并改善衰老引起的膀胱神经肌肉功能变化，这对于减轻与年龄相关的膀胱疾病的影响可能具有重要意义。
