Investigation for roles of prostaglandins in the cerebral facilitatory mechanisms of antidiuretic hormone secretion

1.在清醒大鼠中，静脉输注高渗生理盐水可在15和30分钟后增强血浆抗利尿激素（ADH），并伴有血浆渗透压、钠和氯的增加。在高渗生理盐水输注开始前30分钟，将前列腺素生物合成抑制剂甲氯芬酯局部注射到第三心室前腹侧区（AV3V），可消除ADH反应。甲氯芬酯注射液对血浆ADH以外的其他因子无显著影响。组织学证实，注射部位位于终末椎板血管质内或附近，内侧视前区，脑室周围和正中视前核。PGE2局部应用于这些区域，在5和15分钟后，血浆ADH和动脉压显著升高，但不影响血浆渗透压和电解质。PGE2和甲氯芬酯的这些作用在偶发性注射环时未被观察到，更多的是从AV3V部位偏离到附近的脑室，或者当预定的注射进入脑室时。因此，注入AV3V的药物似乎不太可能通过脑脊液流扩散作用于远离AV3V的区域而产生效果。另一方面，AV3V注射甲氯芬酯对等渗盐水静脉输注期间血浆ADH及其他因素无影响。通过建立放射线免疫分析法，探讨高渗对内源性PGE2水平的影响。大鼠静脉滴注等渗或高渗生理盐水，于0、15、30 min斩首采血。等渗盐水和高渗盐水对血浆PGE2水平均无显著影响。然而，实验前一天植入AV3V的微透析探针获得的间质液中PGE2浓度在高渗盐水输注的前30分钟内呈升高趋势，持续时间超过60分钟。上述结果提示，在AV3V内和/或附近产生的Pgs可能有助于促进高渗状态下ADH的分泌。少

1.In conscious rats iv infusion of hypertonic saline enhanced plasma antidiuretic hormone (ADH) 15 and 30 min later, and this was accompanied by an augmentation of plasma osmolality, sodium and chloride. The ADH response was abolished by local injection of meclofenamate, an inhibitor of prostaglandin biosynthesis, into the anteroventral third ventricular region (AV3V) 30 minbefore the onset of the hypertonic saline infusion. Factors other than plasma ADH were not affected by the meclofenamate injection significantly. The injection sites were confirmed histologically to have been in or near the organum vasculosum of the laminae terminalis, medial preoptic area, and periventricular and median preoptic nuclei. Local applications of PGE2 into such areas caused, 5 and 15 min later, remarkable increases in plasma ADH and arterial pressure, without affecting plasma osmolality and the electrolytes . These effects of PGE2 and meclofenamate were not observed when injection cnnulae were incidenta … More lly deviated from those AV3V sites to the cerebral ventricle near by, or when intended applications into the ventricle were performed. Therefore, it seems unlikely that the drugs administered into the AV3V produced the effects by acting on regions remote from it via diffusion through a stream of cerebrospinal fluid. On the other hand, AV3V injections of meclofenamate were without effect on plasma ADH and the other factors during iv infusion of isotonic saline.2.Effects of hyperosmolality on endogenous PGE2 levels were investigated, by establishing its determination methods by radioimmunoassay. Rats were infused iv with isotonic or hypertonic saline, and were decapitated for bloodcollection at 0,15 and 30 min. Plasma PGE2 level was not affected significantly by either isotonic or hypertonic saline. However, PGE2 concentration in the interstitial fluid obtained through microdialysis probes implanted into the AV3V one day before experiments tended to increase during the first 30 min period of hypertonic saline infusion performed over 60 min.The results mentioned above suggest that Pgs generated in and/or near the AV3V may contribute to facilitation of ADH secretion in the hyperosmotic state. Less