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

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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