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

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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