Hitoshi Hama

Facilitatory role of central dopamine in the osmotic release of vasopressin.

In conscious rats, intracerebroventricular (i.c.v.) injection of the dopamine antagonist haloperidol (0.15 mumol) blocked increases in plasma vasopressin (AVP) and arterial pressure caused by i.c.v. administration of a hypertonic solution (990 mOsm/kg, 10 microliters), without affecting plasma osmolality, electrolytes or hematocrit. The application of the alpha-adrenergic antagonist phenoxybenzamine (0.15 mumol), however, did not significantly inhibit the responses of plasma AVP and arterial pressure to the hypertonic solution. We concluded that brain dopamine may play a facilitatory role in the osmotically stimulated AVP secretion.

Presence of α-neo-endorphin-like immunoreactivity in the posterior lobe of the pituitary gland

Abstract α-neo-endorphin-like immunoreactivity was demonstrated in the nerve fibers and Herrings bodies in the posterior lobe of rat pituitary glands by an indirect immunoperoxidase method using α-neo-endorphin-antiserum. The number of α-neo-endorphin positive fibers and Herrings bodies did not decrease in the sections in which α-neo-endorphin-antisera pretreated with oxytocin, ADH and leu-enkephalin were used as primary antisera. In view of the reports that met-enkephalin, leu-enkephalin and dynorphin were present in the posterior lobe of the pituitary gland, this finding suggested that there were four kinds of opiate-like peptides in the posterior lobes of the pituitary gland. Furthermore, by staining alternately 3he serial sections of the rat pituitary glands with ADH and α-neo-endorphin-antisera, it was revealed that α-neo-endorphin-positive Herrings bodies were identical to a large number of ADH positive Herrings bodies. This finding, together with the observation that morphine injection caused ADH release, suggested that α-neo-endorphin may play an important role in the regulation of ADH release.

A study on the mechanism by which sodium nitroprusside, a nitric oxide donor, applied to the anteroventral third ventricular region provokes facilitation of vasopressin secretion in conscious rats

We reported previously that sodium nitroprusside (SNP) applied to the anteroventral third ventricular region (AV3V), a pivotal area for autonomic functions, facilitates vasopressin (AVP) secretion in conscious rats. The aim of this study was to pursue the problems of whether nitric oxide (NO) generated from the agent may be responsible for the phenomenon, and whether it may be mediated by cyclic guanosine monophosphate (cGMP), the biosynthesis of which could reportedly be activated by NO. The infusion of SNP into the AV3V of conscious rats produced dose-related increases in plasma AVP, the maximal responses of which appeared at 5 min. Blood pressure and heart rate tended to rise at 15 min. The plasma osmolality, sodium, potassium or chloride did not show marked alteration following the SNP administration. Although the SNP solution was hypertonic and hypernatremic, AV3V application of hypertonic saline with a relatively higher osmolality and an equal sodium level was significantly less effective in augmenting plasma AVP. When injected into the lateral ventricle, SNP did not change plasma AVP and reduced arterial pressure, different from the results provoked by the AV3V application. The rise in plasma AVP in response to the AV3V application of SNP was diminished by preadministration of hemoglobin, a scavenger of NO, that did not affect the responses of the other variables. In contrast, pretreatment with methylene blue, an agent capable of antagonizing the potency of NO to activate guanylate cyclase, did not attenuate but potentiated the responses of both plasma AVP and arterial pressure to the AV3V infusion of SNP. Hemoglobin or methylene blue given alone into the AV3V did not affect any of the variables monitored. On the other hand, the AV3V injection of 8-bromo cGMP, a stable analogue of cGMP, was not potent for causing a significant rise in plasma AVP, in contrast to the notable AVP-enhancing effect of 8-bromo cAMP. Arterial pressure and heart rate were elevated by both of these agents, whereas the remaining variables were not altered. Histological inspection indicated that the infusion sites of the drugs in the AV3V had included areas such as the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial preoptic nucleus and periventricular nucleus. On the basis of these results, we concluded that the AVP secretion prompted by the AV3V application of SNP may be attributable to NO, whereas its well-known ability to stimulate guanylate cyclase activity may hardly contribute to this phenomenon.

Adrenal adenomata causing primary aldosteronism

Adenomata taken from 25 patients with primary aldosteronism were observed by electron microscopy. The cells in the adenoma had a well developed agranular endoplasmic reticulum but granular endoplasmic reticulum was not prominent. Most of the mitochondria resembled those in the cells of the zona glomerulosa, suggesting that the adenomata which caused primary aldosteronism are derived from this zone. Spironolactone bodies were found in the cells of the adenoma from a patient who received spironolactone. Their appearance was identical to that descrived in previous reports.

Evaluation for roles of brain prostaglandins in the catecholamine-induced vasopressin secretion in conscious rats.

To evaluate roles of prostaglandins (PGs) in vasopressin (AVP) secretion elicited by stimulating alpha-adrenergic and dopaminergic receptors in the periventricular region, we examined in conscious rats the effects of intracerebroventricular (i.c.v.) injections of a cyclooxygenase inhibitor meclofenamate on the plasma AVP responses to i.c.v. applications of angiotensin II (ANG II), phenylephrine and dopamine. I.c.v. injections of 58 pmol ANG II produced, 5 and 15 min later, augmentations of plasma AVP accompanied by elevations of arterial pressure and tendencies of reduction in heart rate. Similarly, the administrations of 0.53 mumol phenylephrine or dopamine enhanced plasma AVP 5 min later, without altering arterial pressure and heart rate significantly. Meclofenamate (0.31 mumol) applied i.c.v. 30 min prior to the administrations of ANG II remarkably inhibited the AVP and pressor responses to this peptide. However, the responses of plasma AVP, arterial pressure and heart rate to phenylephrine or dopamine were not affected by the i.c.v. administrations of 0.31 mumol meclofenamate. The injections of meclofenamate followed by the administrations of a vehicle for ANG II and the catecholamines were without effect on plasma AVP and the cardiovascular parameters. Plasma osmolality, sodium, potassium and chloride in all the groups mentioned above were not significantly changed during experiments. These results suggest that PGs generated in the periventricular region, despite their probable stimulatory roles in the ANG II-evoked AVP secretion, may not participate in the AVP-releasing mechanisms activated by dopaminergic and alpha-adrenergic receptors, supporting the view that PGs and the catecholamines may facilitate AVP release via separate pathways.

Separation of periventricular dopaminergic and α-adrenergic systems from the vasopressin-secreting mechanisms activated by prostaglandin D2

The aim of this study was to evaluate periventricular dopaminergic and alpha-adrenergic receptor functions in vasopressin (AVP) secretion elicited by central applications of prostaglandin D2 (PGD2) in conscious rats. Intracerebroventricular (i.c.v.) injections of PGD2 (70.9 nmol (25.0 micrograms] produced transient rises in plasma AVP 5 min later, without increasing plasma osmolality, sodium and hematocrit. Arterial pressure and heart rate before and after the PGD2 administrations were not significantly different from those of control rats receiving its vehicle. The PGD2-induced AVP response was not significantly altered by the prior i.c.v. administrations (0.15 mumol) of dopamine receptor antagonists, SCH 23390 or sulpiride, and an alpha-adrenoreceptor antagonist, phenoxybenzamine, performed 10 min before the injections of PGD2. The pretreatments with these catecholamine antagonists were confirmed to significantly prevent the augmentations in plasma AVP 5 min after the i.c.v. applications of 0.75 mumol dopamine or phenylephrine that were considerably larger than the PGD 2-induced AVP response. From these results, we concluded that dopaminergic and alpha-adrenergic receptors in the periventricular regions may not be involved in the AVP secretion stimulated by PGD2.

Effect of nephrectomy on angiotensin II concentrations in plasma and hypothalamus of the dehydrated rat

Bilateral nephrectomy in the rats deprived of water for 46 h markedly reduced plasma angiotensin II concentrations (P less than 0.001), but it was without effect on extremely low levels of the hormone in the hypothalamic tissue. These results may suggest that the activity of a possible intrinsic brain renin-angiotensin system is not influenced by that of the kidney-plasma renin-angiotensin system.

Inhibitory role of periventricular dopaminergic mechanisms in hemorrahge-induced vasopressin secretion in conscious rats

Acute blood loss (16 ml/kg b. wt.) in conscious rats caused, 5 min later, increases in plasma vasopressin (AVP) concentration accompanied by reductions in arterial pressure and hematocrit. The plasma AVP response was markedly enhanced by intracerebroventricular injection (10 microliters) of a dopamine antagonist, haloperidol (0.15 mumol), which did not affect the responses of arterial pressure and hematocrit significantly. These results suggest that periventricular dopaminergic mechanisms may act to inhibit hemorrhage-induced AVP secretion.