NOS inhibition enhances myogenic tone by increasing rho-kinase mediated Ca2+ sensitivity in the male but not the female gerbil spiral modiolar artery.
NOS inhibition enhances myogenic tone by increasing rho-kinase mediated Ca2+ sensitivity in the male but not the female gerbil spiral modiolar artery.
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DOI：
10.1371/journal.pone.0053655
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wangemann P
中科院分区：
文献类型：
--
作者：
Reimann K;Krishnamoorthy G;Wangemann P
耳蜗血流调节对于预防缺血和氧化应激引起的听力损失非常重要。耳蜗的血液供应由蜗轴螺旋动脉 (SMA) 提供。在男性中，一氧化氮合酶 (NOS) 阻滞剂 L-NG-硝基精氨酸 (LNNA) 会增强 SMA 的生肌张力，但在女性中则不然。在这里，我们研究了这种性别差异是否基于胞质 Ca2+ 浓度和/或肌丝 Ca2+ 敏感性的差异。使用激光扫描显微镜和显微荧光测定法评估从雄性和雌性沙鼠分离的加压 SMA 节段的血管直径、肌源张力、胞质 Ca2+ 和 Ca2+ 敏感性。在相同血管段中，将 LNNA 诱导的张力的性别差异与 150 mM K+ 和内皮素-1 诱导的张力进行比较，两者均未表现出明显的性别差异。有趣的是，在包括壁内压力变化的方案中观察到了 LNNA 诱导的男性 SMA 张力，但在壁内压力保持恒定时则没有观察到。男性 SMA 中的 LNNA 不会增加平滑肌细胞中的总体 Ca2+ 浓度，但会增加 Ca2+ 敏感性。这种 Ca2+ 敏感性的增加在鸟苷酸环化酶抑制剂 ODQ 存在下或通过外源性应用一氧化氮 (NO) 供体 DEA-NONOate 或 cGMP 类似物 8-pCPT-cGMP 被消除。 rho 激酶阻滞剂 Y27632 降低了男性 SMA 的基础 Ca2+ 敏感性，并消除了 LNNA 诱导的 Ca2+ 敏感性增加。 LNNA 和 Y27632 均未改变女性 SMA 的 Ca2+ 敏感性。数据表明，LNNA 诱导的音调中的性别差异是基于 rho 激酶介导的 Ca2+ 敏感性调节中的性别差异。因此，Rho 激酶和 NO 成为调节耳蜗血流的关键因素。男性 SMA 中 NO 依赖性机制的更大作用预示着在内皮细胞功能受损的情况下对耳蜗血流的更大限制。
Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-NG-Nitro-Arginine (LNNA) in males, but not in females. Here, we investigated whether this gender difference is based on differences in the cytosolic Ca2+ concentration and/or the Ca2+ sensitivity of the myofilaments. Vascular diameter, myogenic tone, cytosolic Ca2+, and Ca2+ sensitivity were evaluated in pressurized SMA segments isolated from male and female gerbils using laser-scanning microscopy and microfluorometry. The gender difference of the LNNA-induced tone was compared, in the same vessel segments, to tone induced by 150 mM K+ and endothelin-1, neither of which showed an apparent gender-difference. Interestingly, LNNA-induced tone in male SMAs was observed in protocols that included changes in intramural pressure, but not when the intramural pressure was held constant. LNNA in male SMAs did not increase the global Ca2+ concentration in smooth muscle cells but increased the Ca2+ sensitivity. This increase in the Ca2+ sensitivity was abolished in the presence of the guanylyl cyclase inhibitor ODQ or by extrinsic application of either the nitric oxide (NO)-donor DEA-NONOate or the cGMP analog 8-pCPT-cGMP. The rho-kinase blocker Y27632 decreased the basal Ca2+ sensitivity and abolished the LNNA-induced increase in Ca2+ sensitivity in male SMAs. Neither LNNA nor Y27632 changed the Ca2+ sensitivity in female SMAs. The data suggest that the gender difference in LNNA-induced tone is based on a gender difference in the regulation of rho-kinase mediated Ca2+ sensitivity. Rho-kinase and NO thus emerge as critical factors in the regulation of cochlear blood flow. The larger role of NO-dependent mechanisms in male SMAs predicts greater restrictions on cochlear blood flow under conditions of impaired endothelial cell function.
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影响因子：
64.8
作者：
BOLOTINA, VM;NAJIBI, S;COHEN, RA
通讯作者：
COHEN, RA
影响因子：
8.3
作者：
Chrissobolis, S;Budzyn, K;Sobey, CG
通讯作者：
Sobey, CG
影响因子：
4.8
作者：
Sauzeau, V;Le Jeune, H;Loirand, G
通讯作者：
Loirand, G
DOI：
10.1073/pnas.91.16.7583
发表时间：
1994-08-02
影响因子：
11.1
作者：
ARCHER, SL;HUANG, JMC;WEIR, EK
通讯作者：
WEIR, EK
影响因子：
8.3
作者：
de Wit, C;Jahrbeck, B;Pohl, U
通讯作者：
Pohl, U