Department of Biomedical Science, Bond University, Queensland 4229, Australia.
Eur J Pharmacol. 2012 Jan 15;674(2-3):445-9. doi: 10.1016/j.ejphar.2011.11.020. Epub 2011 Nov 19.
In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue.
在膀胱中，一氧化氮 (NO) 从神经元和非神经元来源释放，但它的作用尚不清楚。尿路上皮加固有层条带对激动剂有反应并发生自发的相收缩，本研究的目的是研究 NO 对这种活性的影响。来自猪膀胱的分离的尿路上皮/固有层条带自发收缩（3.5±0.3 个周期/分钟），并对卡巴胆碱和电刺激（EFS）收缩。一氧化氮合酶抑制剂 N(ω)-硝基-L-精氨酸 (L-NNA，100μM) 对组织没有影响，但一氧化氮供体二乙胺 NONO 盐 (DEANO，100μM) 和硝普盐 (10μM) 导致松弛，降低自发收缩率并抑制对卡巴胆碱的反应。DEANO 和硝普盐分别使卡巴胆碱引起的最大强直收缩减少 17±4%（P<0.001）和 35±5%（P<0.001），卡巴胆碱的效力也降低。卡巴胆碱还增加了收缩的自发频率，这些速率反应再次被 DEANO 和硝普盐抑制，但不受 L-NNA 影响。同样，EFS 的反应被 DEANO 显著抑制（52-70%）（P<0.05），但不受 L-NNA 影响。这些数据表明尿路上皮和固有层中存在自发收缩活性以及神经和激动剂诱导的紧张性收缩活性。这种活性对一氧化氮的抑制敏感，但一氧化氮似乎不是自发释放来影响这种活性，也似乎不是由毒蕈碱受体刺激释放。然而，结果表明，在一氧化氮产生增加的情况下，一氧化氮可以影响该组织的收缩活性。
