|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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
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