Medicinal Chemistry and Drug Action, Department of Pharmaceutical Biology and Pharmacology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.
J Urol. 2012 Jun;187(6):2254-60. doi: 10.1016/j.juro.2012.01.072. Epub 2012 Apr 13.
We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates.
Conventional intracellular microelectrode and tension recording techniques were used.
The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p<0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p<0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p<0.05).
The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.
我们研究了一氧化氮对幼年和老年豚鼠前列腺自发性活动的抑制作用。
采用常规细胞内微电极和张力记录技术。
一氧化氮供体硝普钠（10μM）消除了 5 个幼年和 5 个老年前列腺中的自发性收缩和慢波活动。加入一氧化氮合酶抑制剂 L-NAME（10μM）后，每个年龄组的自发性收缩和电活动频率均显著增加。年轻组（约 40%至 50%）比老年组（约 10%至 20%）的增加更为显著（2 因素方差分析，p<0.01）。其他测量参数，包括自发性电和收缩活动的持续时间、幅度和膜电位，与对照值无差异。鸟苷酸环化酶抑制剂 ODQ（10μM）使 6 个幼年豚鼠前列腺的自发性活动频率增加 10%至 30%（学生配对 t 检验，p<0.05）。然而，它对老年前列腺没有影响。cGMP 类似物 8-Br-GMP（1μM）和 PDE5 抑制剂双嘧达莫（1μM）使 4 至 9 个年轻和老年前列腺中的收缩活动频率显著降低约 70%（学生配对 t 检验，p<0.05）。
与年轻前列腺组织相比，老年前列腺组织对 L-NAME 诱导的自发性收缩和慢波活动反应减弱，提示随着年龄的增长，一氧化氮的产生减少。这可能进一步解释了与年龄相关的前列腺特异性疾病中观察到的前列腺平滑肌张力增加，如良性前列腺增生。
