Possible roles of prostaglandins in the anteroventral third ventricular region in the hyperosmolality-evoked vasopressin secretion of conscious rats

Abstract

This study explored the roles of prostaglandins in the anteroventral third ventricular region, a cerebral osmoreceptor site, in the osmoregulation mechanism of vasopressin release. We injected (1 microliter) prostaglandin E2 (12.8 nmol) or meclofenamate (78.3 nmol), an inhibitor of prostaglandin biosynthesis, into the brain region or the lateral cerebral ventricle of conscious rats, examining their effects on plasma vasopressin and its controlling factors in the presence or absence of an osmotic stimulus. The injection of prostaglandin E2 into the anteroventral third ventricular region augmented plasma vasopressin and arterial pressure after 5 min and 15 min, without influencing plasma osmolality, sodium, potassium, or chloride. In contrast, intraventricular injection of prostaglandin E2 did not cause any significant effect on those variables. The i.v. infusion (0.1 ml.kg-1.min-1) of hypertonic saline (2.5 mol/l) enhanced plasma vasopressin after 15 min and 30 min; this was accompanied by increased plasma osmolality, sodium, and chloride, and by unaltered or elevated arterial pressure. Meclofenamate given into the anteroventral third ventricular region 30 min before starting the hypertonic saline infusion abolished the osmotic vasopressin response without significantly changing the responses of the other variables. Histological analysis showed that the injection sites of meclofenamate in these rats were close to those of prostaglandin E2 in the anteroventral third ventricular region and included the organum vasculosum of the lamina terminalis and the surrounding area, the medial preoptic area, and periventricular and median preoptic nuclei. When injection cannulae for meclofenamate deviated from those areas incidentally or when the drug was expressly administered into the cerebral ventricle, the osmotic vasopressin response was not inhibited. Plasma vasopressin and the other variables observed during the i.v. infusion of isotonic saline (0.15 mol/l) were not affected significantly by meclofenamate administration into the anteroventral third ventricular region or the cerebral ventricle. On the basis of these results, we concluded that prostaglandins synthesized in and/or near the anteroventral third ventricular region might contribute to the facilitation of vasopressin release in the hyperosmotic state.

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

“…Approximately 1 min elapsed before withdrawing the infusion tubing, so as to permit drug movement away from its tip. The doses of meclofenamate and PGE 2 were determined in view of previous studies (2,22). The donor blood was prepared on the day of experiments by collecting into a heparinized beaker (150 U/rat) the trunk blood issuing after decapitation of normal rats anesthetized lightly with diethyl ether.…”

“…2), implying that the attenuation of the AVP response may not be explained by the difference in the depressor response capable of stimulating AVP release. In view of the remarkable augmentation of brain PGs by bleeding (9) and their central actions in promoting AVP release (2,7,(10)(11)(12)22), it is probable that endogenous PGs generated in the brain tissue may be involved in AVP secretion in response to hypotensive and nonhypotensive hemorrhages.…”

“…3), despite the lack of effect of this prostanoid when given at a double dose into the extra-AV3V tissue or i.c.v. (22). Accordingly, it seems reasonable to postulate AV3V or its neighborhood as one site of action of endogenous PGs in contributing to hemorrhage-induced AVP secretion.…”

“…Neurons in the AV3V receive afferent input from the brainstem regions such as the A1 cell group and the parabrachial nucleus which are implicated in transmission of peripheral pressurevolume information (14)(15)(16)(17). The AV3V neurons send efferent fibers to the AVP neurosecretory cells in the hypothalamic paraventricular and supraoptic nuclei, and play pivotal roles in regulating AVP release and cardiovascular function (14,(18)(19)(20)(21)(22). In addition to these neuroanatomical features, it is known that the AV3V is equipped with immunoreactive material like cyclooxygenase (23), a PG synthetase, and a high density of PGE 2 -binding sites (24).…”

“…In addition to these neuroanatomical features, it is known that the AV3V is equipped with immunoreactive material like cyclooxygenase (23), a PG synthetase, and a high density of PGE 2 -binding sites (24). Furthermore, it has been suggested that augmentation of PGE 2 production in the AV3V, which might be caused by bleeding (9), may lead to acceleration of AVP release (22). Therefore, it is conceivable that PGs synthesized in the AV3V may be involved in the hypovolemia-evoked AVP secretion.…”