Maggi C A, Evangelista S, Grimaldi G, Santicioli P, Giolitti A, Meli A
J Pharmacol Exp Ther. 1984 Aug;230(2):500-13.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and endogenous arachidonic acid (AA) depletion on spontaneous and drug-induced contractions of the rat urinary bladder have been determined by both in vivo and in vitro experiments. Our results suggest that some AA metabolites (presumably prostaglandins) are involved in the physiologic regulation of the micturition reflex in the rat. In vivo findings indicate that the ability of various NSAIDs to inhibit distension-induced rhythmic contractions is proportional to their anti-inflammatory effectiveness. NSAIDs administration or depletion of endogenous AA at the detrusor muscle level by essential fatty acid-free diet (EFAFD) decreased the responsiveness of the urinary bladder to reflex activation. Topical AA triggered a series of neurogenic rhythmic contractions in the preparation which failed to respond to saline loading. This effect was prevented by NSAID pretreatment. The effect of topical AA was mimicked in NSAID-treated preparations by topical prostaglandins. Both NSAIDs and EFAFD reduced the responsiveness of the rat urinary bladder to acetylcholine and purinergic stimulation in vivo and in vitro. NSAIDs enhanced, while EFAFD reduced, the responsiveness of the isolated bladder to stable cholinomimetics. Responsiveness to KCl was unaffected by NSAIDs or EFAFD. These latter findings indicate that either blockade of AA metabolism along the cyclooxygenase pathway or endogenous AA depletion might alter bladder responsiveness at the postjunctional level. However, because the amplitude of distension-induced rhythmic contractions is unaffected by NSAIDs or EFAFD, it appears unlikely that endogenous prostanoids play a role in excitatory neurotransmission or in tension development during physiological-like activation of the bladder muscle. In vitro findings indicate that both NSAIDs and EFAFD reduce the myogenic contractility and the responsiveness to stretch of bladder muscle. These findings are suggestive that AA metabolites could regulate micturition by enhancing the amplitude of the myogenic contractions of the bladder muscle and, consequently, the discharge of vesical afferents to the central nervous system.
通过体内和体外实验，已确定非甾体抗炎药（NSAIDs）和内源性花生四烯酸（AA）耗竭对大鼠膀胱自发收缩和药物诱导收缩的影响。我们的结果表明，一些AA代谢产物（可能是前列腺素）参与大鼠排尿反射的生理调节。体内研究结果表明，各种NSAIDs抑制扩张诱导的节律性收缩的能力与其抗炎效果成正比。在逼尿肌水平给予NSAIDs或通过无必需脂肪酸饮食（EFAFD）耗竭内源性AA会降低膀胱对反射激活的反应性。局部应用AA会在该制剂中引发一系列神经源性节律性收缩，而该制剂对盐水灌注无反应。NSAIDs预处理可防止这种效应。在NSAIDs处理的制剂中，局部应用前列腺素可模拟局部应用AA的效应。NSAIDs和EFAFD在体内和体外均降低了大鼠膀胱对乙酰胆碱和嘌呤能刺激的反应性。NSAIDs增强了分离膀胱对稳定拟胆碱药的反应性，而EFAFD则降低了这种反应性。对氯化钾的反应性不受NSAIDs或EFAFD的影响。这些最新研究结果表明，沿环氧化酶途径阻断AA代谢或内源性AA耗竭可能会改变节后水平的膀胱反应性。然而，由于扩张诱导的节律性收缩幅度不受NSAIDs或EFAFD的影响，因此内源性前列腺素似乎不太可能在膀胱肌肉生理性激活期间的兴奋性神经传递或张力发展中发挥作用。体外研究结果表明，NSAIDs和EFAFD均降低了膀胱肌肉的肌源性收缩力和对拉伸的反应性。这些研究结果提示，AA代谢产物可能通过增强膀胱肌肉的肌源性收缩幅度，从而调节排尿，进而调节膀胱传入神经向中枢神经系统的放电。
