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

1.本研究的目的是揭示一氧化氮(NO)在第三脑室前腹侧区(AV3V)的作用，探讨其在该地区血浆高张或PGE_2升高中的作用。通过对清醒大鼠的实验，得到了以下结果：1.一氧化氮合酶底物L-精氨酸(Arg)注入AV3V可刺激ADH分泌，使血压和心率升高，而L-Arg的立体异构体D-Arg对上述指标无明显影响。这些药物对血浆渗透压、Na~(++)、K~(++)和Cl~(-3)均无影响。预先输注一氧化氮合酶抑制剂L-NAME可使ADH、BP和HR的反应消失，单独应用L-NAME对ADH的释放无影响，但可使基线血压和心率升高。AV3V注射NO的自发释放剂硝普钠(SNP)也可促进ADH的释放。BP增加更多…与L-精氨酸组比较，E明显减慢，HR等其他指标无明显变化。SNP刺激ADH释放的效果优于高渗氯化钠在AV3V.5中的作用。预先输入血红蛋白可抑制SNP对ADH释放的影响，但不影响SNP的升压作用。相反，亚甲蓝(MB)预处理可增强SNP对ADH和BP.6的影响。向AV3V内注入cGMP后，ADH释放量增加，血压和心率增加，与L-Arg组相同。将L或D-精氨酸注入房室结附近区域并不改变监测的所有变量。脑室给药时，L-精氨酸刺激ADH释放，硝普钠降低血压，其他变量不变。AV3v静注L-NAME不影响AV3v静注PGE_2所致的ADH释放、血压和心率的增加。同样，对静脉注射的反应。AV3V L不影响ADH和BP的高渗氯化钠输注，也不影响血浆渗透压、Na+和Cl2-的输注。这些结果表明，AV3V产生的NO可能至少部分地通过激活cGMP的合成来增加ADH的释放、血压和心率，但在渗透压或PGE2刺激存在的情况下，它可能在控制这些变量中不起重要作用。较少

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