Possible participation of prostaglandins generated in the anteroventral third ventricular region in the hypovolemia-induced vasopressin secretion of conscious rats

Department of Physiology, Niigata University School of Medicine, Niigata City, Japan.

OBJECTIVE: The aim of this study was to investigate the roles of prostaglandins (PGs) in the anteroventral third ventricular region (AV 3V), a cerebral site for cardiovascular homeostasis, in hypovolemia-induced vasopressin (AVP) secretion. METHODS: We infused meclofenamate (78. 3 nmol in 1 microl), a PG synthesis inhibitor, or PGE2 (7.1 nmol in 0.5 microl) into the AV 3V of conscious rats, examining their effects on plasma AVP and other variables in the presence or absence of hemorrhages. The hemorrhages (about 14% of blood volume) were conducted successively by taking femoral arterial blood over a 30-s period at 10-min intervals. RESULTS: The first hemorrhage increased plasma AVP in blood samples obtained 10 min later, without affecting plasma angiotensin II (ANG II), arterial pressure and heart rate. The second hemorrhage after 10 min raised plasma AVP further and, remarkably, augmented plasma ANG II, and reduced arterial pressure. The AVP responses to both the first and second hemorrhages were attenuated by meclofenamate infusion into the AV 3V performed 35 min before the first hemorrhage. The meclofenamate infusion did not alter the response of ANG II, while that of arterial pressure was potentiated and heart rate was decreased after the second hemorrhage. These effects of meclofenamate on plasma AVP and the cardiovascular parameters were not found when the drug was infused into the nucleus accumbens, the region slightly distant from the AV 3V, or the lateral cerebral ventricle. In the normovolemic state, meclofenamate administered into the three brain regions did not affect any of the variables monitored. In contrast, application of PGE2 into the AV 3V enhanced plasma AVP, heart rate and arterial pressure after 5 and 15 min. Histological examination indicated that infusion sites of meclofenamate in the AV 3V were close to those of PGE2 in several cases and included areas such as the organum vasculosum of the lamina terminalis, periventricular hypothalamic nucleus, and the median and medial preoptic nuclei. CONCLUSION: These results suggest that PGs synthesized in and/or near the AV 3V may be involved in the regulation of AVP release and cardiovascular function in the hypovolemic state.