Evaluation for functional correlation between prostaglandins and dopamine in regulation mechanisms of ADH release in the AV3V

1. 本研究旨在探讨低血容量状态下第三心室前腹侧区（AV3V）合成的前列腺素（PGs）在ADH释放和心血管系统中的调节机制，以及AV3V儿茶酚胺受体在介导PGE2应答中的作用。实验在有意识的大鼠中进行，并长期植入大脑和血管插管。从股动脉抽取体重1%的血液两次（H1和H2）。H1升高血浆ADH (pADH)，但不影响动脉压（AP）和心率（HR），而H2进一步升高血浆ADH， AP明显下降，血浆血管紧张素II （ANGII）明显升高。这些出血不改变血浆渗透压或钠，但增加血浆氯化物和降低血浆钾。在AV3V中局部注入PG合成抑制剂甲氯芬酯（MCL）可阻止pADH对出血的反应，增强AP的反应，并导致H2后HR的显著降低。血浆ANGII等其他变量不受MCL的影响。当MCL注入离AV3V稍远的伏隔核或脑室时，不会产生这些影响。当PGE2应用于MCL输注点附近AV3V部位时，pADH、AP、HR均显著升高。在AV3V中局部输注多巴胺（DA）和肾上腺素激动剂苯肾上腺素（PHE）可引起短暂的pADH增强。DA对其他变量没有影响，而PHE的应用在大约50%的测试中导致AP的同时升高。AV3V输注β -肾上腺素能激动剂异丙肾上腺素诱导的降压和心动过速效应。通过事先将α -肾上腺素能拮抗剂phenoxybenzamine应用于AV3V， PHE对pADH和AP的影响被消除。DA对pADH的作用可被D1-DAergic拮抗剂SCH23390阻断，但不能被D2-DAergic拮抗剂舒必利阻断。单独使用这些拮抗剂不影响包括pADH.7在内的任何变量。AV3V输注苯氧苄胺、SCH23390和舒必利对pge2诱导的pADH、AP和hr无显著影响。这些结果表明，在AV3V中形成的PGs可能在调节ADH释放、AP和HR中发挥重要作用，而PGE2对这些因素的影响可能不是由AV3V儿茶酚胺受体介导的，尽管它们能够影响这些因素。少

1. The aims of reseach project were to examine roles of prostaglandins (PGs) synthesized in the anteroventral third ventricular region (AV3V) in regulation mechanisms of ADH release and cardiovascular system under hypovolemic condition, and to evaluate those of AV3V catecholamine receptors in mediating responses to PGE2. Experiments were conducted in conscious rats with cerebral and vascular cannulae implanted chronically.2. Blood of 1% of body weight was removed twice (H1 and H2) from the femoral artery. H1 increased plasma ADH (pADH) without affecting arterial pressure (AP) and heart rate (HR), whereas after H2 further augmentation of pADH were produced with conspicuous falls in AP and rises in plasma angiotensin II (ANGII). These homorrhages did not alter plasma osmolality or sodium, but increased plasma chloride and decreased plasma potassium.3. An inhibitor of PG synthesis meclofenamate (MCL) infused locally into the AV3V prevented the pADH responses to the bleeding, potentiated t … More hose of AP, and caused singnificant reduction of HR following H2. Other variable such as plasma ANGII were not influenced by MCL.These effects of MCL were not caused when it was infused into the nucleus accumbens, a region sligtlhy distant from the AV3V,or into the cerebral ventricle.4. When PGE2 was applied into the AV3V sites near infusion points of MCL,pADH,AP and HR increased singnificantly.5. Local infusion of dopamine (DA) and an alpha-adrenegic agonist phenylephrines (PHE) into the AV3V elicited transient augmentation of pADH.DA influenced none of the other variables, whereas PHE application caused concomitant reises of AP in approximately 50% of tests. The AV3V infusion of a beta-adrenergic agonist isoproterenol induced depressor and tachycardiac effects.6. The effects of PHE on both the pADH and AP were abolished by prior application of an alpha-adrenergic antagonist phenoxybenzamine into the AV3V.The effect of DA on pADH was blocked by the prior administration of a D1-DAergic antagonist SCH23390, but not by that of a D2-DAergic antagonist sulpiride. The application of these antagonists alone did not affect any of the variables including pADH.7. The AV3V infusion of phenoxybenzamine, SCH23390 and sulpiride were without significant effect on the PGE2-evoed responses of pADH,AP and HR.8. These results suggest that PGs formed in the AV3V may play important roles in regulating ADH release, AP and HR,and that the effects of PGE2 on these factors may not be mediated by AV3V catecholamine receptors, despite their ability to influence the factors. Less