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

1. 本研究旨在揭示一氧化氮（NO）在前腹侧第三心室区（AV3V）中的作用，并探讨其是否在该区域血浆高渗或PGE2升高的情况下发挥作用。通过清醒大鼠的实验得到如下结果：一氧化氮合酶（NOS）底物l -精氨酸（Arg）注入AV3V后可刺激ADH分泌，提高动脉压（BP）和心率（HR），而l -精氨酸的立体异构体d -精氨酸（D-Arg）对上述指标无显著影响。这些药物不影响血浆渗透压、Na^+、K^+或Cl^- 3。预灌注NOS抑制剂L-NAME可抑制ADH、BP和HR对L-Arg的反应。AV3V单独应用L-NAME并不影响ADH的释放，尽管它提高了基线血压和hr。AV3V输注硝普钠（SNP），一氧化氮的自然释放物，也促进ADH的释放。与输注l -精氨酸组相比，血压升高更慢，而HR等其他变量没有变化。在AV3V.5中，SNP刺激ADH释放的效力与高渗NaCl相当。预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。相比之下，亚甲基蓝（MB）预处理增强了SNP对ADH和bp的影响。注入AV3V后，cGMP导致ADH释放升高，与L-Arg组相比，血压和HR升高。L-或D-Arg给予接近AV3V的区域并没有改变所有被监测的变量。当在脑室内应用时，l -精氨酸刺激ADH释放，SNP降低血压，其他变量不变。AV3V输注L-NAME不影响AV3V输注PGE2引起的ADH释放、血压和HR升高。同样，静脉输注ADH和BP高渗NaCl的反应，以及血浆渗透压、Na^+或Cl^-的反应也不受AV3V l - name的影响。这些结果表明，AV3V中产生的NO可能至少部分通过激活cGMP合成来增加ADH释放、BP和HR，但在渗透或PGE2刺激存在时，它可能在控制这些变量方面发挥不重要作用。少

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