Plasma Arginine Vasopressin Levels Research Articles

Age-dependent cardiovascular, renal and endocrine responses to furosemide in conscious lambs.

1. The present study was performed to investigate some of the physiological responses to furosemide during postnatal maturation. 2. In 1- (n = 8) and 6-week old (n = 10) conscious, chronically instrumented lambs at least 3 days after surgery, three experiments were performed at intervals of 24-48 h and in random order. Various parameters of cardiovascular and endocrine function, as well as cumulative urinary flow rates, were measured before and after intravenous injection of 0 mg/kg (experiment one), 0.25 mg/kg (experiment two; low dose) and 5 mg/kg (experiment three; high dose) furosemide. 3. After high-dose furosemide, mean venous pressure decreased and there was a transient increase in mean arterial pressure in lambs aged 6 weeks. At 1 week of age, heart rate increased after high-dose furosemide and renal blood flow decreased. After high-dose furosemide, plasma renin activity increased in both groups of lambs, although the effects were greater in 1-week-old lambs. Plasma levels of arginine vasopressin increased after high-dose furosemide in lambs aged 1 but not 6 weeks. Cumulative urinary flow rate responses to furosemide were similar in 1- and 6-week-old lambs. 4. These data provide new information that cardiovascular and endocrine responses to furosemide are developmentally regulated.

The effect of the maze procedure on the secretion of arginine-vasopressin and aldosterone

Background Excessive fluid retention is a serious complication after the maze procedure that cannot be totally explained by changes in levels of atrial natriuretic peptide. We therefore measured circulating levels of arginine vasopressin and aldosterone in patients undergoing the maze procedure to study their possible role in this postoperative complication. Methods Serial arginine vasopressin and aldosterone levels were monitored for 72 hours in 11 patients after coronary artery bypass grafting and in 13 patients after the maze procedure. Hemodynamic data, urine output, fluid balance, and complications were recorded prospectively during the same period of time. Results Plasma levels of arginine vasopressin and aldosterone were significantly higher in patients after the maze procedure when compared with patients after coronary artery bypass grafting. Conclusions This study documents that the maze procedure results in increased plasma arginine vasopressin and aldosterone levels and indicates that they, rather than atrial natriuretic peptide alone, participate in the excessive postoperative fluid retention that follows the maze procedure. We believe that these hormone elevations are most likely secondary to a temporary lack of response of the atrial baroreceptors. These results may explain the effectiveness of spironolactone therapy after the maze procedure.

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency.

Hyponatremia occurs not infrequently in hypopituitarism. Arginine vasopressin (AVP)-induced impaired water excretion is found in patients with hypopituitarism and experimental models of glucocorticoid deficiency. The present study was undertaken to determine whether augmented release of AVP is involved in the development of hyponatremia in elderly subjects with secondary adrenal insufficiency. Forty patients with ACTH-deficient, secondary adrenal insufficiency were examined. They were divided into three groups according to the age at which diagnosis was ascertained (group A <20 Years, group B 20-64 Years, and group C>or=65 Years). Hyponatremia was more manifest in the elderly group than in the other two groups, serum sodium (Na) levels being 124.7 mmol/l in the elderly group, a value significantly less than 141.5 and 133.5 mmol/l in groups A and B. Plasma AVP levels seemed likely to be high compared with the respective hypo-osmolality in plasma in the elderly group, as plasma AVP levels were 1.7 pmol/l despite a mean plasma osmolality of 259 mmol/kg. Such an alteration was less clear in group B and was not found in group A. Therefore, elevation of plasma AVP was apparent in the elderly patients. Hydrocortisone replacement promptly normalized serum Na levels from 125 to 142 mmol/l (P<0.01) and reduced plasma AVP levels from 1.7 to 0.9 pmol/l (P<0.05), which were comparable to the respective plasma osmolality in the elderly patients. These results indicate that non-suppressible release of AVP is crucially involved in the impaired water excretion and hyponatremia seen in elderly patients with secondary adrenal insufficiency compared with the younger patients, and that exaggerated release of AVP becomes manifest as the subjects grow older.

Urinary Concentration Defect and Limited Expression of Sodium Cotransporter, rBSC1, in a Rat Model of Chronic Renal Failure

Background: Renal urinary concentration is associated with enhanced expression of sodium cotransporter (rBSC1) in thick ascending limb of Henle. Overexpression of rBSC1 was reported recently in hypertrophied nephrons after unilateral nephrectomy (UNX) and in kidney isografts. Since urinary concentration defect and hypertrophy of residual nephrons are major manifestations of chronic renal failure (CRF), we investigated the rBSC1 signals for RNA and protein in a rat model of CRF. Methods: Rats underwent 5/6 nephrectomy and examined 8 weeks after operation. rBSC1 mRNA was examined by competitive PCR and in situ hybridization, and rBSC1 protein signals by western blotting and immunohistochemistry. Rats that underwent sham-operation, UNX, or 5/6 nephrectomy followed by a 3-week recovery period (acute renal failure), were used as control. Water intake was restricted for 24 h in subgroups of control and CRF rats. Results: Microscopic examination showed hypertrophy of residual nephrons in both UNX and CRF rats. Signals for rBSC1 mRNA and protein were enhanced at basal condition only in rats with UNX. Under basal conditions, CRF rats demonstrated low urinary osmolality in spite of high plasma arginine vasopressin levels. Water restriction resulted in increased signals for rBSC1 mRNA and protein and concentration of urine in sham-operated rats, but such increases were absent and urinary concentration was incomplete in CRF rats. Conclusions: Compensatory overexpression and upregulation of rBSC1 expression in response to dehydration are both absent in CRF rats. These limitations are thought to be the underlying mechanisms of urinary concentrating defect seen in CRF.

Alterations of Renal Vasopressin V1A and V2 Receptors in Spontaneously Hypertensive Rats

To elucidate the role of arginine vasopressin (AVP) in a hypertensive state, the characteristics of renal cortex V_1A and medulla V₂ receptors in young spontaneously hypertensive rats (SHR) during the developmental phase of hypertension were compared with those of age-matched Wistar-Kyoto (WKY) rats using the radioligand receptor assay technique. The systolic blood pressure of 8-week-old SHR was statistically significantly higher than that of WKY rats (142 ± 1 vs. 125 ± 2 mm Hg). The plasma AVP levels were also significantly higher in SHR than in WKY rats (3.20 ± 0.41 vs. 1.96 ± 0.34 pg/ml). In SHR, the maximum capacity of ³H-d(CH₂)₅Tyr(Me)AVP binding to cortical V_1A receptors (B_max) was statistically significantly higher than that of WKY rats (39.7 ± 2.7 vs. 22.4 ± 0.9 fmol/mg protein). Furthermore, the B_max values of ³H-AVP binding to medullary V₂ receptors in SHR were also significantly higher than in WKY rats (40.2 ± 1.9 vs. 28.3 ± 1.3 fmol/mg protein). However, the apparent dissociation constant (K_d) values of renal cortex V_1A and medulla V₂ receptors in SHR and WKY rats were not significantly different. These results indicate that increased amounts of renal cortex V_1A and medulla V₂ receptors in SHR play an important role in the pathophysiology of hypertension.

Prolonged prenatal hypernatremia alters neuroendocrine and electrolyte homeostasis in neonatal sheep.

Arginine vasopressin (AVP) is a neuroendocrine hormone synthesized in the hypothalamus, and is stored and secreted by the posterior pituitary gland in response to stimuli such as plasma hypertonicity and hypotension. The primary physiologic roles of AVP include plasma osmolality and blood pressure regulation. We have previously demonstrated that chronic prenatal plasma hypertonicity alters the AVP regulatory pathway in newborn lambs. The objectives of the present study were to evaluate prolonged effects of antenatal plasma hypertonicity on neonatal plasma osmoregulation. Pregnant ewes at 119 +/- 3 days of gestation were water restricted to achieve and maintain hypertonicity until normal-term delivery. After delivery, ewes were provided food and water ad libitum and lambs were allowed maternal nursing. At the age of 28 days, blood samples were obtained for the analysis of plasma osmolality, electrolytes, and AVP levels from study (n= 5) and age-matched control (n= 6) lambs. Subsequently, lambs were euthanized, and the pituitary and hypothalamus were processed for the determination of pituitary AVP content by radioimmunoassay, and AVP gene expression by Northern analysis. In response to water restriction, maternal plasma osmolality significantly increased (306 +/- 1.1 to 326 +/- 1.2 mOsm/kg, P< 0.001). At the age of 28 days, plasma sodium level was higher in study (prenatally dehydrated) than control lambs (144.6 +/- 0.4 vs 142.6 +/- 0.3,P< 0.05). Study lambs had higher plasma AVP concentrations than the control lambs (4.1 +/- 0.4 vs 1.7 +/- 0.4 pg/ml,P< 0.05). Similarly, total pituitary AVP content was higher in thein utero hypertonic lambs than in the control lambs (6.5 +/- 1.0 vs 2.8 +/-1.2 microg, P< 0.05). However, there was no difference in hypothalamic AVP mRNA levels between the two groups. The present study demonstrates that chronic maternal and fetal plasma hypertonicity has prolonged effects on pituitary and plasma AVP, as well as plasma sodium in neonatal lambs, providing further evidence suggesting prenatal imprinting of osmoregulation through at least 1 month of age.

INCREASED EXPRESSION OF AQUAPORIN WATER CHANNELS IN HYPOTHYROID RAT KIDNEY

The present study was aimed to determine the molecular mechanisms underlying the water retention associated with hypothyroidism. Male Sprague–Dawley rats (200–220 g) were experimentally induced of hypothyroidism by treatment with methimazole in drinking water (0.04%) for 8 weeks. In the experimental group, serum concentrations of thyroxine and triiodothyronine were significantly decreased. The expression of aquaporin 2 (AQP2) was significantly increased in the cortex, outer medulla, and inner medulla of the kidney. The expression of AQP1 as well as that of AQP3 was significantly increased in the cortex, though not in the medulla. The adenylyl cyclase activity provoked by arginine vasopressin (AVP), sodium fluoride, or forskolin was blunted in the hypothyroid kidney, while plasma levels of AVP were not significantly changed. The increased expression of AQP1–3 channels may in part account for the water retention in hypothyroidism.

Glomerular and tubular responses to N(G)-nitro-L-arginine methyl ester are age dependent in conscious lambs.

The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged approximately 1 (n = 8) and approximately 6 wk (n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME; experiment 1) or its inactive isomer D-NAME (experiment 2). After administration of L-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by approximately 50% at 20 min, remaining decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after L-NAME. Proximal fractional Na(+) reabsorption decreased after L-NAME administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was sustained for 60 min. There were no effects of L-NAME on proximal fractional Na(+) reabsorption in 1-wk-old lambs. In 6-wk-old lambs, urinary flow rate increased by approximately 500%, free water clearance increased by approximately 50%, and urinary osmolality decreased by approximately 60% after L-NAME administration; no effects on these variables were measured in 1-wk-old lambs. The diuresis after L-NAME administration to 6-wk-old lambs was unaccompanied by any changes in plasma levels of arginine vasopressin. There were no effects of D-NAME on any of the measured variables. We conclude that endogenously produced nitric oxide modulates glomerular and tubular function in an age-dependent manner.

Urinary Excretion of Aquaporin-2 Water Channel in Diabetic Ketoacidosis

We studied the changes in plasma arginine vasopressin (AVP) and urinary excretion of aquaporin-2 (UAQP-2) water channel in 3 patients with diabetic ketoacidosis. They had marked hyperglycemia of 27.9 ± 2.8 mmol/l (mean ± SEM), and elevated hemoglobin A1c of 8.8 ± 1.4%. Circulatory blood volume was decreased by approximately 25%, which was determined by the changes in hematocrit. Plasma AVP levels were elevated to 10.3 ± 3.0 pmol/l and UAQP-2, 578 ± 200 fmol/mg creatinine (normal, 153 ± 28) at the hospitalization. When hyperglycemia was improved by the intravenous infusion of a small dose of insulin plus fluid administration, both plasma AVP and UAQP-2 promptly decreased to 1.2 ± 0.2 pmol/l and 252 ± 29 fmol/mg creatinine on day 7, respectively. These alterations were concomitant with the recovery of circulatory blood volume. In the present study, UAQP-2, in addition to plasma AVP, indicates circulatory blood volume depletion, and the changes in UAQP-2 estimates the AVP-dependent recovery of circulatory blood volume during the therapeutic period in the patients with diabetic ketoacidosis.

Adaptation to sustained high plasma vasopressin in water and electrolyte homeostasis in the rat transgenic for the metallothionein-vasopressin fusion gene.

Prolonged exposure of tissues to a receptor agonist often leads to adaptive changes that limit the subsequent responsiveness of the tissue to the same agonist. Recently, we have generated rats transgenic for the metallothionein I-human arginine vasopressin (AVP) fusion gene (Tg), which produced high plasma AVP with relatively preserved renal water excretion, suggesting that there might be adaptive mechanism(s) for maintaining water and electrolyte homeostasis against chronic AVP oversecretion from the earliest stage of life. In this study, to investigate whether down-regulation of AVP V2 receptor (V2R), which could possibly be caused by long-standing high plasma AVP, participates in this adaptive mechanism(s), non-peptidic V2R antagonist OPC31260 was administered to reverse the down-regulation, and water loading was performed after V2R antagonist treatment had been withdrawn. Additionally, to confirm the down-regulation, Northern blotting analysis for V2R mRNA was carried out. Tg rats showed slightly decreased urine volume and water intake with an equivalent plasma [Na(+)] level (Tg 140.4 +/- 0.6 mEq/l; control 139.3 +/- 0.6 mEq/l) under basal conditions. After water loading using a liquid diet containing zinc, which stimulates the promoter region in the transgene, the urine increase showed only limited suppression with a dramatically increased plasma AVP level and mild hyponatremia (135.8 +/- 1.8 mEq/l) in Tg rats. When diet containing OPC31260 had been provided for 4 days until the day before the start of water loading, antidiuresis and hyponatremia (125.4 +/- 1.mEq/l) were significantly potentiated. V2R mRNA expression in kidney was significantly less in Tg rats than in control rats under basal conditions, and this suppression was restored by OPC31260 treatment to levels comparable with those of control rats. These results suggest that long-standing high plasma AVP causes V2R down-regulation, and it may play an important role in the adaptive mechanism(s) for maintaining water and electrolyte homeostasis in chronically AVP-overexpressing rats.

Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene.

Arginine vasopressin (AVP) is a major antidiuretic hormone, the overproduction of which causes diluting hyponatremia in humans and is called the syndrome of inappropriate antidiuresis (SIAD). To study physiological changes resulting from AVP overproduction and to develop an animal model of hyponatremia, the human AVP gene was expressed under the control of the metallothionein promoter in transgenic (Tg) rats. Analyses of AVP immunoreactivity (irAVP) in the tissues revealed that the transgene is expressed mainly in the central nervous system. Gel filtration showed that irAVP in the brain and plasma was properly processed AVP. AVP purified from the brains of both Tg and control rats also exerted equal bioactivity to generate cAMP in LLC-PK1 cells. The founder rats did not show any physical or anatomical abnormalities. Under basal conditions, Tg rats had high plasma AVP levels (Tg 13.8 +/- 2.5 pg/ml; control 2.7 +/- 1.2 pg/ml; n=6 in both groups; means +/- S.E.M.), decreased urine volume, and normal plasma [Na(+)]. Hypertonic saline injected i.p. did not affect AVP secretion in Tg rats. In response to a zinc-supplemented liquid diet, plasma AVP decreased in control rats, but increased in Tg rats (Tg 32.7 +/- 2.7 pg/ml; control 1.0+/-0.1 pg/ml; n=6), resulting in hyponatremia (Tg 135.2 +/- 2.5 mEq/l; control 140.8 +/- 0.4 mEq/l; n=6). To our knowledge, this is the first transgenic animal to show diluting hyponatremia. This transgenic rat may therefore provide a useful model in which to investigate various physiological alterations resulting from the oversecretion of AVP which involve SIAD, stress response, behavior, and blood pressure.

Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the DeltaE47 neurophysin mutation.

Postmortem examinations of the hypothalamus of patients with autosomal dominant neurohypophyseal diabetes insipidus (adNDI), which have been reported only on persons dying between the ages of 37-87 yr, reveal the presence of the arginine vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the expected AVP-producing magnocellular neurons. To determine whether the clinical course of adNDI is compatible with the hypothesis that the neuropathologic findings are attributable to a progressive loss of magnocellular neurons beginning in early life, we performed posterior pituitary magnetic resonance imaging and water deprivation tests, including plasma ACTH measurements, on 17 affected members of a kindred with the deltaE47 neurophysin mutation whose ages ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr) underwent these tests as controls. All six children undergoing magnetic resonance imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of nine affected adults showed an absent or barely visible PPHS, whereas eight of nine age-matched nonaffected adults produced a normal size PPHS. During water deprivation tests, infants concentrated their urine normally, and a 3-month-old infant produced a high plasma AVP level of 15.7 pmol/liter. By school age, affected children were no longer able to concentrate their urine or prevent hypernatremia. Affected adults became dehydrated; their median plasma AVP level was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P = 0.008). These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.

Changes in serum sodium, sodium balance, water balance, and plasma hormone levels as the result of pelvic surgery in women.

Postoperative hyponatremia in women has been associated with the development of serious neurological disorders and even death, with a predisposition for menstruant women. The objective of this study was to evaluate the immediate hormonal, water and electrolyte responses to pelvic surgery in both pre and postmenopausal women. Of the twenty-five consecutive women studied, twenty were premenopausal while five were postmenopausal. Mean age was 45.4 +/- 1.6 years. Measurements of plasma renin activity, follicular stimulating hormone and luteinizing hormone showed no significant change pre to postoperatively. There was a significant decrease in pre to postoperative values of estrogen, 97.4 +/- 20.3 to 36.3 +/- 7.5 pg/mL (p < 0.05). There was also a significant decline in postoperative values for plasma aldosterone and plasma progesterone. Data were similar in pre and postmenopausal patients. Serum sodium levels decreased from 141.5 +/- 0.5 to 137.2 +/- 0.5 mEq/L (p < 0.01). During the twenty-four hours following surgery, mean net sodium balance was positive 122 mEq and mean measured fluid balance was positive 1108 mL. Ringers lactate or normal saline were used. On the first postoperative day, plasma arginine vasopressin levels were elevated at 4.0 +/- 0.8 pg/mL, with a mean urine osmolality of 504 +/- 29 mOsm/kg H2O. The data illustrate that women undergoing pelvic surgery decrease their serum sodium in the immediate postoperative period. Despite both positive sodium and water balance, there is a stronger tendency to conserve water. Decreased estrogen levels occur and this decrease may facilitate brain cell adaptation to plasma hypotonicity. Since the administration of isotonic fluid will not protect against the decrease in serum sodium, postoperative sodium concentration should be carefully monitored.

Analyses of factors contributing to vulnerability to antenatal periventricular leukomalacia induced by hemorrhagic hypotension in chronically instrumented fetal sheep.

Our purpose was to determine factors contributing to vulnerability to antenatal periventricular leukomalacia (PVL) induced by hemorrhagic hypotension in premature fetal sheep. Systemic hypotension was induced in 10 fetal sheep by acutely withdrawing 35% to 40% of the fetoplacental blood volume at 113 d gestation. Brains were processed for histologic analysis 6 d after the insult. Statistical comparisons of physiologic parameters between fetuses suffering from PVL (n = 5) and those without PVL (n = 5) were performed. Significant correlations were found between induction of PVL and fetal brain weight, changes in fetal mean blood pressure over time, base excess, oxygen content, hematocrit, and plasma arginine vasopressin (AVP) levels in fetal abdominal aortic blood. Brain developmental stage, the magnitude of induced systemic hypotension, and baseline blood oxygen content were important intrinsic factors in the induction of antenatal PVL by hemorrhagic hypotension in premature fetal sheep.

Posture-related tachycardia in older patients with hyponatremia

Hyponatremia (HN) is the commonest electrolyte abnormality in elderly patients. Its etiology in this setting is poorly understood. In this study, the authors aim to compare the hemodynamic and hormonal responses of a group of older patients with a predisposition to HN with a group of age-matched controls. We assessed hemodynamic and hormonal responses to postural challenge in 15 patients over age 65 with serum sodium concentrations of less than 130 mM (mean 128.7 mM) and 15 age-matched controls with normal sodium concentrations. Patients remained recumbent for 1 h and stood for the second. Blood was drawn at baseline and at 15 min intervals. Blood pressure (BP) and pulse rates (PR) were monitored electronically. Plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), renin and aldosterone were determined periodically during the study period. No difference in BP between groups was noted. PR increased significantly in the HN group only within 3 min of standing (from 71±4 to 86±5, P<0.01) and remained significantly higher than controls until 90 min (87±5 vs. 69±4, P<0.01). While plasma AVP levels increased significantly following 30 min standing and remained elevated for both HN and control groups, it did not differ significantly between the two. Baseline plasma ANP levels were significantly higher in HN patients compared with controls and remained significantly higher ( P<0.05) throughout the study. There was no significant difference in plasma renin or aldosterone levels between groups during the study period. We have demonstrated differing autonomic and hormonal responses to orthostatic challenge between HN patients and age-matched controls. Water retention due to the syndrome of inappropriate anti-diuretic hormone secretion (with reset osmostat) may lead to raised ANP levels in this older cohort of patients. Further physiological studies are required to clarify the precise mechanism of these varying responses.

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans.

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

Urinary excretion of the aquaporin-2 water channel exaggerated in pathological states of impaired water excretion.

The present study was undertaken to determine whether the hydro-osmotic action of arginine vasopressin (AVP) is exaggerated in pathological states of impaired water excretion by measuring urinary excretion of the aquaporin-2 (AQP-2) water channel. Eighteen hyponatraemic patients with impaired water excretion and 12 control subjects were studied during an acute oral water load (20 ml/kg body weight). In the patient group plasma AVP levels were 1.6 pmol/l, relatively high compared to plasma osmolality of 279.8 mmol/kg. Urinary excretion of AQP-2 under ad libitum water drinking was 41.1 fmol/micromol creatinine in the patient group, a value significantly greater than that of 21.7 fmol/micromol creatinine in the control subjects. The acute water load verified the impairment in water excretion in the patient group, as the excretion of the water load was only 28.2% (control, 77.3%, P < 0.001) and the minimum urinary osmolality was as high as 437.3 mmol/kg (control, 122.9 mmol/kg, P < 0.001). Also, the minimum urinary excretion of AQP-2 was significantly greater in the patient group than that in the control. There was a positive correlation between plasma AVP levels and urinary excretion of AQP-2 in the control subjects (r = 0.56, P < 0.01). In contrast, the urinary excretion of AQP-2 was exaggerated compared to the respective plasma AVP levels in the patient group, and thus the positive correlation disappeared. These results indicate that hydroosmotic action of AVP is exaggerated more than that expected from plasma AVP levels in pathological states of impaired water excretion, with non-suppressible, but normal, arginine vasopressin levels in spite of the hypo-osmotic condition.

Close Association of Urinary Excretion of Aquaporin-2 with Appropriate and Inappropriate Arginine Vasopressin-Dependent Antidiuresis in Hyponatremia in Elderly Subjects1

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP) in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old) during the last 5-yr period. Subjects were separated into euvolemic hyponatremia groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with hyponatremia was derived from hypopituitarism, but severe hyponatremia was found in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the elderly. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis in the 3 groups of patients, except for one miscellaneous one. An acute water load test verified the impairment in water excretion, because the percent excretion of the water load was less than 42% and the minimal urinary osmolality was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2 were not reduced after the water load. The inappropriate secretion of AVP was evident in the patients with SIADH and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP-2 and renal water excretion in those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to compensate loss of body fluid in the patients with mineralocorticoid-responsive hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean). Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects.

Vasopressin pressor receptor-mediated activation of HPA axis by acute ethanol stress in rats.

The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress-induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH.

Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients

Respective contributions of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) to the urinary sodium concentration were evaluated in 23 naturalistic incidents of polydipsia-hyponatremia observed in 11 hospitalized schizophrenics (10 males and 1 female). The sodium concentration of the spontaneously excreted urine was examined before and after the forced water restriction. Before the water restriction, mean (±S.D.) plasma ANP was 52.8±33.9 pg/ml (range=6.9–137). Plasma AVP levels were below 0.3 pg/ml in 15 episodes; relatively high levels (≥0.3) were noted in eight episodes. Means of urinary sodium concentration (mEq/l) were significantly higher in episodes with high AVP (≥0.3) alone (25.0±8.2, n=4), with high ANP (>43) alone (21.3±7.4, n=9), and with high AVP and ANP (26.8±6.4, n=4) as compared to that of the low AVP (<0.3) and ANP (≤43) group (13.5±3.7, n=6). The data indicate that the elevated urinary sodium in polydipsic patients is possibly due to the AVP-induced antidiuresis and/or the ANP-induced natriuresis. In addition, we observed a close relationship between elevated plasma AVP and vomiting, suggesting that vomiting is one of the causal factors responsible for AVP elevations in this syndrome.