Intraventricular administration of arginine vasopressin suppresses prolactin release via a dopaminergic mechanism

The present study was conducted to determine the effects of intracerebroventricular administration of arginine vasopressin (AVP) on the preovulatory prolactin (PRL) surge. Hourly injections of 1 or 5 micrograms AVP from 1200 to 1700 hr on proestrus prevented increases in plasma PRL levels that afternoon. However, following cessation of AVP treatment, a marked increase in PRL levels occurred between 1830 and 2030 hr. This "rebound" secretion of PRL was greater in rats given 5 micrograms AVP than in rats given the lower dose. The suppression of PRL release by AVP appears to be mediated by dopamine since 5 micrograms AVP failed to inhibit PRL release in animals pretreated with the dopamine antagonist domperidone. Interestingly, under these conditions, AVP increased PRL release compared to levels observed in saline-treated rats. In addition to suppressing PRL release, AVP exerted a dose-dependent inhibition of preovulatory LH release. The results suggest a possible interaction between AVP and dopamine in controlling PRL release which likely takes place within the median eminence.     

Arginine vasopressin, circulation, and kidney during graded water immersion in humans

Ten normal males rested sitting upright at an air temperature of 28 degrees C for 5.5 h (control, C) and underwent 4 h of graded water immersion (WI) to the umbilicus (UI), to the chest (CI), and to the neck (NI), respectively (water temperature = 34.5 degrees C), on different experimental days. Plasma arginine vasopressin (PAVP) was suppressed during WI compared with C and maximally so during NI. However, there was no change in PAVP comparing CI with UI even though central venous pressure (CVP) increased. CVP increased during CI and NI compared with C but was unchanged during UI, whereas cardiac output (rebreathing method), stroke volume, and plasma volume increased to approximately the same level during all three steps of WI compared with C. Heart rate and total peripheral vascular resistance decreased during UI, CI, and NI. Systolic arterial pressure (SAP) and pulse pressure (PP) were increased gradually from prestudy related to the degree of WI. Also diuresis, natriuresis, kaliuresis, osmotic excretion, and clearance were increased gradually compared with C, whereas free water clearance (CH2O) gradually decreased. There were weak negative but statistically significant correlations between PAVP and CVP and between changes in PAVP from prestudy and corresponding changes in SAP and PP. Furthermore, a statistically significant and negative correlation between CH2O and natriuresis could be established. We conclude that graded immersion gradually increases central blood volume and decreases PAVP. However, not only cardiopulmonary mechanoreceptors but also arterial baroreceptors may play a role in AVP suppression during WI in humans. In hydropenic subjects the suppression of PAVP during WI is apparently not effective in counteracting the decrease in CH2O induced by increased solute excretion.     

Catecholamines, circulation, and the kidney during water immersion in humans

Because results in literature are discrepant with regard to the effects of water immersion (WI) on the release of norepinephrine (NE) in humans, the following study was performed. Simultaneous measurements of plasma NE, central cardiovascular variables, and renal sodium excretion were conducted in eight normal male subjects on 2 study days; 6 h of thermoneutral (35.0 degrees C) WI to the neck were preceded and followed by 1 h in the seated posture outside the water and 8 h of a seated control period. During the control period, the subjects wore a water-perfused garment (water temperature 34.6 degrees C) to obtain the same skin temperature as during WI. The subjects were fluid restricted overnight and kept in this condition throughout the study. Compared with the prestudy, post-study, and control periods, plasma NE decreased significantly by 61% during WI. Simultaneously, central venous pressure, cardiac output, stroke volume, systolic arterial pressure, and arterial pulse pressure increased, whereas heart rate decreased. Renal sodium excretion and urine flow rate increased. In conclusion, the release of NE is suppressed in humans during immersion. This decrease probably reflects a decrease in sympathetic nervous activity initiated by stimulation of low- and high-pressure baroreceptors. It is possible that the decrease in NE acts as one of several mechanisms of the natriuresis and diuresis of immersion in humans.     

Effects of dehydration on the vasopressin response to immersion

Nine healthy volunteers underwent three experimental procedures in random order. The protocols were 4 h of thermal dehydration followed by 2 h of head-out water immersion, 4 h of thermal dehydration followed by 2 h of chair rest, and 6 h of rest in the supine position. Four hours of heat exposure (50 degrees C) resulted in a body weight loss of approximately 3.5%. Plasma osmolality rose by approximately 5 mosmol/kg, mean arterial pressure (MAP) decreased from 85 to 78 mmHg, and body temperature increased from 36.8 to 38.6 degrees C. As a consequence of the combined action of hypertonicity, hypovolemia, hypotension, and hyperthermia, plasma arginine vasopressin (AVP) increased from 2.1 to 8.1 pg/ml after 4 h thermal dehydration. Changes in body weight, plasma osmolality, body temperature, and MAP were similar after either a subsequent 2 h of water immersion or 2 h of chair rest. However, during chair rest plasma AVP remained elevated (8.4 pg/ml), whereas during immersion plasma AVP decreased from 8.1 to 4.7 pg/ml. This was probably due to the central hypervolemia induced by immersion. Our results support the hypothesis that central hypervolemia rather than hypotonicity is the primary stimulus for AVP suppression during water immersion in dehydrated subjects. During the early immersion period hypoosmolality might contribute to the AVP suppression.     

Vasopressin release in response to hypovolaemia in the conscious rat and the effect of opioid and aminergic receptor antagonists.

Conscious rats were given i. p. polyethylene glycol (PEG) or dextran injections to compare their efficacy in inducing moderate hypovolaemia. Dextran was found unsuitable, producing large variability in the plasma vasopressin (AVP) concentrations. Putative neurotransmitters involved in the AVP response to hypovolaemia and in basal release were examined using opioid, and beta-adrenoceptor and dopamine receptor-blocking agents. A dose of PEG was chosen to produce a decrease in blood volume of approx 14.5% giving plasma AVP concentrations of 19.0 +/- 4.6 pmol/l. Naloxone and phenoxybenzamine failed to influence AVP release under both hypovolaemic and basal conditions. Prazosin also failed to influence the AVP response. In contrast propranolol elevated the plasma AVP concentrations in both conditions. Haloperidol enhanced basal AVP release but did not influence release during hypovolaemia. Guanethidine pretreatment partially blocked the response to hypovolaemia, but did not affect basal plasma AVP. Thus it appears that aminergic pathways have an inhibitory influence on AVP release under hypovolaemic and basal conditions. However, endogenous opioids do not appear to contribute significantly to the hypovolaemic response.     

Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were approximately 20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.     

Central venous pressure and plasma arginine vasopressin in man during water immersion combined with changes in blood volume

To investigate the influence of central venous pressure (CVP) changes on plasma arginine vasopressin (pAVP), 8 normal male subjects were studied twice before, during and after immersion to the neck in water at 35.1 degrees +/- 0.1 degrees C (mean +/- SE) for 6 h. After 2 h of immersion, blood volume was either expanded (WIEXP) by intravenous infusion of 2.0 1 of isotonic saline during 2 h or reduced by loss of 0.5 1 of blood during 30 min (WIHEM). The two studies were randomised between subjects. WIEXP increased CVP, systolic arterial pressure (SAP), diuresis, natriuresis, kaliuresis and osmolar clearance compared to WIHEM while haematocrit, haemoglobin concentration and urine osmolality decreased. Heart rate, mean arterial (MAP) and diastolic arterial pressure, plasma osmolality, plasma sodium, plasma potassium and free water clearance did not differ significantly in the two studies. pAVP was significantly higher after 6 h in WIHEM than after 6 h in WIEXP (2.0 +/- 0.2 vs. 1.6 +/- 0.2 pg X ml-1, mean +/- SE; P less than 0.05). pAVP values were corrected for changes in plasma volume due to infusion in order properly to reflect AVP secretion. In conclusion, there was a weak, but significant, negative correlation between CVP and pAVP during the two studies, while during recovery from WIHEM and WIEXP decrements in SAP and MAP correlated significantly and strongly with increases in pAVP. It is therefore concluded that it is the arterial baroreceptors rather than the cardiopulmonary mechanoreceptors which are of importance in AVP regulation in man.     

Baroreceptor-mediated suppression of osmotically stimulated vasopressin in normal humans

Increases in central venous pressure and arterial pressure have been reported to have variable effects on normal arginine vasopressin (AVP) levels in healthy humans. To test the hypothesis that baroreceptor suppression of AVP secretion might be more likely if AVP were subjected to a prior osmotic stimulus, we investigated the response of plasma AVP to increased central venous pressure and mean arterial pressure after hypertonic saline in six normal volunteers. Plasma AVP, serum osmolality, heart rate, central venous pressure, mean arterial pressure, and pulse pressure were assessed before and after a 0.06 ml.kg-1.min-1-infusion of 5% saline give over 90 min and then after 10 min of 30 degrees head-down tilt and 10 min of head-down tilt plus lower-body positive pressure. Hypertonic saline increased plasma AVP. After head-down tilt, which did not change heart rate, pulse pressure, or mean arterial pressure but did increase central venous pressure, plasma AVP fell. Heart rate, pulse pressure, and central venous pressure were unchanged from head-down tilt values during lower-body positive pressure, whereas mean arterial pressure increased. Plasma AVP during lower-body positive pressure was not different from that during tilt. Osmolality increased during the saline infusion but was stable throughout the remainder of the study. These data therefore suggest that an osmotically stimulated plasma AVP level can be suppressed by baroreflex activation. Either the low-pressure cardiopulmonary receptors (subjected to a rise in central venous pressure during head-down tilt) or the sinoaortic baroreceptors (subjected to hydrostatic effects during head-down tilt) could have been responsible for the suppression of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Centrally administered galanin modifies vasopressin and oxytocin release from the hypothalamo-neurohypophysial system of euhydrated and dehydrated rats.

Galanin (Gal) as a neuropeptide with widespread distribution in the central nervous system may be involved in the mechanisms of vasopressin (AVP) and oxytocin (OT) release from the hypothalamo-neurohypophysial system. Vasopressin and oxytocin content in the hypothalamus and neurohypophysis as well as plasma level of both neurohormones were studied after galanin treatment in euhydrated and dehydrated rats. In not dehydrated rats intracerebroventricular (i.c.v.) injections of Gal did not affect the hypothalamic and neurohypophysial OT content, however, distinctly increased plasma OT concentration. In the same animals Gal diminished the hypothalamic AVP content but was without the effect on neurohypophysial AVP storage; plasma AVP level then raised. Galanin, administered i.c.v. to rats deprived of water, distinctly inhibited AVP and OT release from the hypothalamo-neurohypophysial system. Simultaneously, plasma AVP and OT level was significantly diminished after Gal treatment in dehydrated rats. These results suggest that modulatory effect of galanin on vasopressin and oxytocin release depends on the actual state of water metabolism. Gal acts as an inhibitory neuromodulator of AVP and OT secretion under conditions of the dehydration but stimulates this process in the state of equilibrated water metabolism.     

Angiotensin II attenuates the natriuresis of water immersion in humans

The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). min(-1) (WI + ANG II-low), and 3) a seated time control (Con). In another almost identical protocol, 7-10 healthy young males were investigated to delineate the tubular site(s) of action of ANG II by the lithium clearance method (C(Li)) and were on an additional fourth study day subjected to infusion of ANG II at a rate of 1.5 ng. kg(-1). min(-1) (WI + ANG II-high). During WI + placebo, plasma concentration of ANG II decreased from 16 +/- 2 to 8 +/- 1 pg/ml (P < 0.05) and renal sodium excretion increased from 104 +/- 15 to 294 +/- 27 micromol/min (P < 0.05). During WI + ANG II-low, plasma ANG II was not suppressed by WI, and the natriuresis was blunted by 52 +/- 13% (P < 0.05). During WI + ANG II-low and WI + ANG II-high, an increase in C(Li) was prevented that was otherwise observed during WI, and fractional distal reabsorption of sodium was facilitated. In conclusion, maintaining plasma concentration of ANG II unchanged at the level of control attenuates the natriuresis of WI considerably in humans. Therefore, suppression of generation of ANG II is an important mechanism of the natriuresis of WI in humans. Furthermore, infusion of ANG II during WI prevents an otherwise induced increase in C(Li) and facilitates the fractional distal reabsorption of sodium, probably via an effect on aldosterone release.     

Effect of TRH on plasma arginine vasopressin

Effect of thyrotropic releasing hormone (TRH) on plasma arginine vasopressin (AVP) was studied in human subjects. All 7 normal controls and 2 hypothyrotropic hypothyroid subjects failed to show any rise of AVP on TRH administration. The 4 primary hypothyroid subjects had elevated basal AVP level and showed further elevation on TRH administration. Our data suggests that elevated TRH in primary hypothyroid subjects may act directly as a nonosmotic stimulus or modulate the osmoreceptor and hypothalamic neurohypophyseal system for AVP release.     

Atrial natriuretic peptide is only a minor diuretic factor in dehydrated subjects immersed to the neck in water

To determine if the atrial natriuretic peptide (ANP) is an important factor for inducing diuresis during head-out water immersion even in dehydrated subjects, six healthy volunteers were immersed up to the neck in water at 34.5 degrees C for three hrs. Significant diuresis and natriuresis occurred, but urine osmolality decreased and negative CH2O was restored in a positive direction toward zero, even though subjects were still in a state of considerable dehydration. Plasma renin activity and plasma angiotensin I and II concentrations decreased but that of plasma aldosterone remained unchanged during water immersion, and plasma ANP did not increase throughout the examination. On the basis of the data of the present study, the factor inducing diuresis during head-out water immersion in hydrated subjects appears to differ from that in dehydrated subjects, and the main factor inducing diuresis during water immersion in dehydrated subjects may be the suppression of vasopressin release and not ANP.     

Vasopressin and blood pressure regulation

The vasoconstrictor actions of arginine vasopressin (AVP) have been shown to occur in concentrations much lower than previously thought. Pressor responses to AVP are a poor index of vasoconstrictor activity since, in contrast to other vasoconstrictor agents, the expected rise of pressure is offset by dose-dependent decreases of cardiac output. The mechanisms for this appear to be, in large part, modulation of the autonomic nervous system whereby AVP enhances vagal nerve activity and reduces peripheral sympathetic nerve activity. AVP enhancement of baroreceptor reflex gain is in part responsible for these changes in some species (dog and rabbit), but not in others (rat). The release of AVP appears to contribute significantly to the normalization of arterial pressure in volume-depleted and hypotensive states. The link between plasma AVP and hypertension remains unclear, but it appears likely that it has an important permissive action in the development of sodium-dependent forms of hypertension.     

Arterial pulse pressure and vasopressin release during graded water immersion in humans

Previous results indicate that arterial pulse pressure modulates release of arginine vasopressin (AVP) in humans. The hypothesis was therefore tested that an increase in arterial pulse pressure is the stimulus for suppression of AVP release during central blood volume expansion by water immersion. A two-step immersion model (n = 8) to the xiphoid process and neck, respectively, was used to attain two different levels of augmented cardiac distension. Left atrial diameter (echocardiography) increased from 28 +/- 1 to 34 +/- 1 mm (P < 0.05) during immersion to the xiphoid process and more so (P < 0.05), to 36 +/- 1 mm, during immersion to the neck. During immersion to the xiphoid process, arterial pulse pressure (invasively measured in a brachial artery) increased (P < 0.05) from 44 +/- 1 to 51 +/- 2 mmHg and to the same extent from 42 +/- 1 to 52 +/- 2 mmHg during immersion to the neck. Mean arterial pressure was unchanged during immersion to the xiphoid process and increased during immersion to the neck by 7 +/- 1 mmHg (P < 0.05). Arterial plasma AVP decreased from 2.5 +/- 0.7 to 1.8 +/- 0.5 pg/ml (P < 0. 05) during immersion to the xiphoid process and significantly more so (P < 0.05), to 1.4 +/- 0.5 pg/ml, during immersion to the neck. In conclusion, other factors besides the increase in arterial pulse pressure must have participated in the graded suppression of AVP release, comparing immersion to the xiphoid process with immersion to the neck. We suggest that when arterial pulse pressure is increased, graded distension of cardiopulmonary receptors modulate AVP release.     

Analysis of the vasopressin system and water regulation in genetically polydipsic mice

Polydipsic mice, STR/N, which show extreme polydipsia and polyuria, were discovered in 1958. In the STR/N, urine outputs are much higher than in control mice. The possibility of an abnormal regulation of the arginine vasopressin (AVP) system, or an abnormality in the renal susceptibility to AVP, should be considered. In this study we investigated the AVP system and water regulation in STR/N. We sequenced the AVP and the AVP V(2)-receptor genes of the STR/N by direct sequencing. No mutation was found in either of them. AVP gene expression examined by in situ hybridization and plasma sodium in 8-wk-old STR/N was significantly lower than in control mice, whereas it was significantly higher at 20 wk. Renal sensitivity to injected AVP was attenuated in 20-wk-old STR/N. The suppression of AVP synthesis due to excessive water retention in 8-wk-old STR/N suggests that polydipsia may be the primary cause in this strain. The 20-wk-old STR/N became dehydrated with the acceleration of AVP synthesis, which might have resulted from secondary desensitization to AVP.     

Circulation, kidney function, and volume-regulating hormones during prolonged water immersion in humans.

To investigate whether prolonged water immersion (WI) results in reduction of central blood volume and attenuation of renal fluid and electrolyte excretion, these variables were measured in connection with 12 h of immersion. On separate days, nine healthy males were investigated before, during, and after 12 h of WI to the neck or during appropriate control conditions. Central venous pressure, stroke volume, renal sodium (UNaV) and fluid excretion increased on initiation of WI and thereafter gradually declined but were still elevated compared with control values at the 12th h of WI. Atrial natriuretic peptide (ANP) concentration in plasma initially increased threefold during WI and thereafter declined to preimmersion levels, whereas plasma renin activity, plasma aldosterone, and norepinephrine remained constantly suppressed. It is concluded that, compared with the initial increases, central blood volume (central venous pressure and stroke volume) is reduced during prolonged WI and renal fluid and electrolyte excretion is attenuated. UNaV is still increased at the 12th h of WI, whereas renal water excretion returns to control values within 7 h. The WI-induced changes in ANP, plasma renin activity, plasma aldosterone, and norepinephrine may all contribute to the initial increase in UNaV. The results suggest, however, that the attenuation of UNaV during the later stages of WI is due to the decrease in ANP release.     

Plasma leptin suppression by arginine vasopressin in normal women and men

Leptin inhibits appetite by activating several neuroendocrine systems, including the hypothalamo-pituitary-adrenal cortical (HPA) axis. In turn, elevated glucocorticoids can increase circulating leptin. We therefore measured plasma leptin in 12 normal women and eight normal men administered low-dose physostigmine (PHYSO) and arginine vasopressin (AVP) to stimulate the HPA axis. The subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV), AVP (0.08 U/kg IM), PHYSO + AVP, and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for leptin, adrenocorticotropin (ACTH)1-39, cortisol, and AVP. Estradiol and testosterone also were measured at each test session. PHYSO and AVP produced no side effects in about half the subjects and predominantly mild side effects in the other half, with no significant female-male differences. Correlations between side effects (absent or present) after PHYSO or AVP and the corresponding leptin responses were nonsignificant. Baseline plasma leptin concentrations were significantly higher in the women than in the men (p < 0.003). Leptin concentrations following PHYSO remained unchanged from baseline, indicating that the short-lived ACTH and cortisol increases produced by PHYSO did not affect leptin secretion. In contrast, AVP administration, while also increasing ACTH and cortisol, suppressed leptin, to a significantly greater degree in the women than in the men (p = 0.01). This significant suppression of leptin by AVP has not been previously described; physiologically, it may be part of a negative feedback regulatory system between central leptin and its activation of the HPA axis, by inhibition of leptin production or acceleration of its clearance.     

Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.     

Plasma concentration of antidiuretic hormone in patients with chronic renal insufficiency on maintenance dialysis.

Radioimmunoassay of plasma arginine-vasopressin (AVP) in regularly dialyzed patients with chronic renal insufficiency revealed a parallel increase of AVP and plasma osmolality (POsm) before dialysis (4.16 +/- 0.36 pg/ml and 312.6 +/- 1.80 mOsm/1) and their parallel declin to the normal range (1.93 +/- 0.27 pg/ml and 292.0 +/- 1.27 mOsm/1) during dialysis. Plasma AVP correlated with POsm before and after dialysis (r = 0.611 and 0.453, p less than 0.01 and less than 0.05 respectively). The increase of AVP before dialysis was lower than would correspond to the rise of POsm and lower than that recorded in healthy subjects during dehydration. Statistical correlation between plasma AVP and indicators of body fluid volume changes between or during dialysis were not proved. We found statistical correlation between the mean blood pressure and AVP before dialysis (r = 0.468, p less than 0.05). These findings suggest that in chronic renal insufficiency changes of POsm remain primary regulating factor of AVP secretion. The expansion of extracellular fluid volume has probably only a modifying effect. It remains to be elucidated whether the revealed statistical relationship between the mean blood pressure and AVP before dialysis plays also a pathogenetic role in the development of hypertension in chronic renal insufficiency.