权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Elucidation of Roles for Free Radicals in the AV3V Mechanism Regulating ADH Secretion

阐明自由基在调节 ADH 分泌的 AV3V 机制中的作用

基本信息

批准号：
10670059
负责人：
YAMAGUCHI Ken'ichi
金额：
$ 1.98万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

1. The aim of this research project was to reveal actions of nitric oxide (NO) in the anteroventral third ventricular region (AV3V) and to pursue the problem of whether it may play any roles in the condition with plasma hypertonicity or PGE2 increase in the area. The following results were obtained through experiments in conscious rats.2. Infusion of L-arginine (Arg), the substrate of NO synthase (NOS), into the AV3V stimulated ADH secretion and elevated arterial pressure (BP) and heart rate (HR), while that of D-Arg, the stereoisomer of L-Arg, was without significant effect on these variables. These agents did not affect plasma osmolality, Na^+, K^+ or Cl^-.3. The responses of ADH, BP and HR to L-Arg were abolished by the pre-infusion of a NOS inhibitor L-NAME.The AV3V application of L-NAME alone did not affect ADH release, although it raised baseline BP and HR.4. The AV3V infusion of sodium nitroprusside (SNP), a spontaneous releaser of NO, also promoted ADH release. BP increased mor … More e slowly as compared with the case induced by the L-Arg infusion, while other variables including HR were not altered. The potency of SNP to stimulate ADH release fairly succeeded that of hypertonic NaCl applied into the AV3V.5. The effect of SNP on ADH release was inhibited by the pre-infusion of hemoglobin, while it did not affect the pressor effect of SNP.In contrast, the pretreatment with methylene blue (MB) potentiated the effects of SNP on ADH and BP.6. When infused into the AV3V, cGMP resulted in increases of ADH release, BP and HR as observed in the case of L-Arg infusion.7. L- or D-Arg given into areas close to the AV3V did not change all the variables monitored. When applied intraventricularly, L-arginine stimulated ADH release and SNP lowered BP, leaving other variables unchanged.8. The AV3V infusion of L-NAME did not affect increases of ADH release, BP and HR caused by the AV3V infusion of PGE2. Similarly, the responses to the i.v. infusion of hypertonic NaCl of ADH and BP, as well as those of plasma osmolality, Na^+ or Cl^-, were not influenced by AV3V L-NAME.9. These results suggest that NO generated in the AV3V may act to increase ADH release, BP and HR via, at least in part, activation of cGMP synthesis, but it may not play an essential role in controlling such variables in the presence of osmotic or PGE2 stimulus. Less

1.本研究的目的是揭示一氧化氮（NO）在前腹侧第三脑室区（AV 3V）的作用，并探讨它是否在该区域血浆高渗或PGE 2升高的条件下发挥任何作用。通过对清醒大鼠的实验，获得了以下结果.向AV 3V内注入NO合成酶（NOS）的底物L-精氨酸（Arg）可刺激ADH分泌，升高动脉压（BP）和心率（HR），而L-精氨酸的立体异构体D-精氨酸（D-Arg）对上述指标无明显影响。这些药物不影响血浆渗透压、Na^+、K^+或Cl^-。预先输注NOS抑制剂L-NAME可阻断ADH、BP和HR对L-Arg的反应，AV 3V单独应用L-NAME不影响ADH的释放，但可升高基线BP和HR. AV 3V输注硝普钠（SNP），一种自发的NO释放剂，也促进ADH的释放。血压升高莫尔 ...更多信息 e慢于L-Arg输注诱导的情况，而其他变量包括HR没有改变。SNP刺激ADH释放的效力相当成功地与应用于AV 3V.5的高渗氯化钠相当成功。预先输注血红蛋白可抑制SNP对ADH释放的影响，但不影响SNP的升压作用;而预先输注亚甲基蓝（MB）可增强SNP对ADH和BP的作用.当输注到AV 3V时，cGMP导致ADH释放增加，BP和HR增加，如在L-Arg输注的情况下所观察到的。L-或D-Arg进入区域附近的AV 3V没有改变所有的变量监测。当心室内应用L-精氨酸时，L-精氨酸刺激ADH释放，SNP降低血压，而其他变量不变。AV 3V输注L-NAME不影响PGE 2引起的ADH释放、血压和心率的增加。同样，静脉注射高渗NaCl对ADH和BP的反应，以及对血浆渗透压、Na^+或Cl^-的反应，也不受AV 3V L-NAME的影响。这些结果表明，在AV 3V中产生的NO可以通过至少部分激活cGMP合成来增加ADH释放、BP和HR，但在渗透压或PGE 2刺激的存在下，它可能在控制这些变量中不起重要作用。少