Serum Arginine Vasopressin Levels Research Articles

#3314 DIURETIC AND RENOPROTECTIVE EFFECTS OF GOREISAN IN A RAT MODEL OF NEPHROTIC SYNDROME

Abstract Background and Aims Goreisan, a traditional Chinese medicine composed of five herbs, is commonly used for the purpose of control of edema and gastrointestinal symptoms. However, the detailed mechanisms have not been fully elucidated. In clinical settings, nephrotic syndrome often causes edema, mainly due to hypoalbuminemia and sodium retention. Thus, we investigated the effects of Goreisan on the kidney using a rat model of nephrotic syndrome. Method A model of nephrotic syndrome was created by a right nephrectomy and subsequent administration of adriamycin using Sprague Dawley rats. Nephrotic rats were randomly divided into three groups at 10 weeks of age as follows; vehicle (control), Goreisan 0.5 g/kg (GL), and Goreisan 1.0 g/kg (GH) groups. Goreisan was administered once a day for 4 weeks. At 14 weeks of age, the rats were sacrificed for the evaluation of blood, urine, mRNA expressions, and kidney histopathology. Results Urine volume was significantly increased in the GL and GH groups than in the control group (Δurine volume: control; −1.25±2.48 mL, GL group; 9.83±4.16 mL, GH group; 10.00±2.62 mL). The GH group showed significantly lower urine osmotic pressure compared to the control group. There were no significant differences in urinary sodium excretion and serum arginine-vasopressin levels among the three groups. Subsequently, we assessed the expression of aquaporin (AQP) in kidney tissue using real-time PCR and immunohistochemical staining. The mRNA expression of AQP1, AQP2, AQP3, and AQP4 did not differ among the three groups. However, immunohistochemical staining showed that the localization of AQP2 at the apical plasma membrane of the collecting ducts was decreased by treatment with Goreisan. Furthermore, deterioration of kidney function was prevented by treatment with Goreisan. Histological analysis revealed that glomerular and tubulointerstitial damages were ameliorated in the GL and GH groups compared to the control group (glomerular damage score: control; 2.19±0.05, GL group; 1.71±0.05, GH group; 1.10±0.05, tubulointerstitial damage score: control; 2.55±0.09, GL group; 2.28±0.10, GH group; 2.12±0.10). In addition, urinary 8-OHdG, which is an oxidative stress marker, was significantly lower in the GL and GH groups than in the control group. Conclusion Our results suggested that Goreisan may have diuretic and renoprotective effects by suppressing the trafficking of AQP2 to the apical plasma membrane of the collecting ducts and possibly reducing systemic oxidative stress.

MP03-09 PHENOTYPING NOCTURIA IN HYPERTENSIVES ACCORDING TO 24-HOUR URINE COMPOSITION

You have accessJournal of UrologyCME1 Apr 2023MP03-09 PHENOTYPING NOCTURIA IN HYPERTENSIVES ACCORDING TO 24-HOUR URINE COMPOSITION Joseph Boroda, Susan Gong, Frederick Okoye, Syed Rahman, Matthew Moy, Alla Akivis, Jason Lazar, and Jeffrey Weiss Joseph BorodaJoseph Boroda More articles by this author , Susan GongSusan Gong More articles by this author , Frederick OkoyeFrederick Okoye More articles by this author , Syed RahmanSyed Rahman More articles by this author , Matthew MoyMatthew Moy More articles by this author , Alla AkivisAlla Akivis More articles by this author , Jason LazarJason Lazar More articles by this author , and Jeffrey WeissJeffrey Weiss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There are numerous comorbidities correlated with nocturia, among the most clinically significant of these being hypertension. Elevation in blood pressure (BP) suppresses serum arginine vasopressin levels, lending evidence to the idea that hypertension is associated pathophysiologically with nocturnal polyuria, which may cause nocturia. Greater nighttime BP and lower nocturnal BP dipping have been associated with more frequent nocturnal voiding. The aim of this study is to assess the impact of non-dipping orthostatic BP in hypertensives on nighttime and daytime urine production. METHODS: Participants with a diagnosis of essential hypertension had in-office supine and standing BP recordings and completed 24-hour urine collection and voiding diaries. Urine was collected in 3 containers; one for the first nighttime void, a second for all subsequent nighttime voids and first morning void, and a third for all daytime voids. Participants whose systolic BP decreased with supine positioning were placed in the orthostatic dip group, and participants whose systolic BP increased or was unchanged upon supine positioning were placed in the no orthostatic dip group. RESULTS: There were 12 (9 female) individuals in the dipping group and 19 (13 female) in the non-dipping group. The non-dipping group tended to produce greater volumes of urine both day and night, and had greater 24-hour urine sodium excretion. The sodium concentration of the first nighttime void was significantly higher in the non-dipping group (median: 102; IQR: 76-105 mEq/L) than the dipping group (median: 51; IQR: 32.5 - 65 mEq/L) (p=.024). This urine sodium concentration for the remainder of the night was significantly higher in the non-dipping group (median: 92; IQR: 62-117 mEq/L) than the dipping group (median: 59.5; IQR: 48-77.25 mEq/L) (p=.012). Subjects in the non-dipping group were 79% more likely to experience 2 or more nighttime voids compared to the dipping group (RR: 1.79; 95% CI: 1 – 3.2; p=.052). CONCLUSIONS: An in-office BP measurement that does not dip with supine positioning is associated with more frequent nighttime voiding as well as higher urine concentrations of sodium in both early and late-night voids. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e24 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph Boroda More articles by this author Susan Gong More articles by this author Frederick Okoye More articles by this author Syed Rahman More articles by this author Matthew Moy More articles by this author Alla Akivis More articles by this author Jason Lazar More articles by this author Jeffrey Weiss More articles by this author Expand All Advertisement PDF downloadLoading ...

Secondary oxalosis induced by xylitol concurrent with lithium-induced nephrogenic diabetes insipidus: a case report

BackgroundXylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare.Case presentationA 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient’s consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission.ConclusionsOur patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer’s (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer’s (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury.

L-Carnitine Ameliorates the Decrease of Aquaporin 2 Levels in Rats with Cisplatin-Induced Kidney Injury

Background: It has been found that L-carnitine ameliorated cisplatin-induced acute kidney injury (AKI) in rats. However, the detailed role of L-carnitine in improving the renal urinary concentration function in cisplatin-induced AKI is not fully understood. Methods: In this study, 30 Sprague-Dawley rats were divided randomly into 5 groups: control, cisplatin (CIS), L-carnitine (CAR), L-carnitine plus cisplatin (CAR + CIS), and cisplatin plus L-carnitine (CIS + CAR) groups. Cisplatin (7 mg/kg) and L-carnitine (300 mg/kg) were injected intraperitoneally. Urine (24 h) and blood samples were collected to analyze renal urinary concentrating function. Immunoblotting, confocal laser microscopy, and enzyme-linked immunosorbent assays were used to assess the level and localization of the water channel aquaporin (AQP) 2, and levels of stimulatory G protein α subunit (GSα protein), arginine vasopressin (AVP) receptor 2, adenylyl cyclase and serum AVP. Results: Renal urinary concentrating function was improved by L-carnitine in rats with cisplatin-induced AKI. AQP2 expression, which decreased after cisplatin treatment, was improved by L-carnitine in different regions of the kidney. Moreover, our data indicated that L-carnitine could increase AQP2 accumulation at the apical plasma membranes of the renal-collecting ducts. Finally, intervention with L-carnitine effectively improved the expression of AQP2 upstream signaling proteins, such as GSα protein, adenylyl cyclase, and serum AVP levels in rats with cisplatin-induced AKI. Conclusion: L-carnitine resolves the cisplatin-induced urinary concentration defect, which may occur by increasing AVP/cyclic adenosine monophosphate/AQP2 levels, indicating the potential use of L-carnitine to ameliorate the renal urinary concentration effect in cancer patients treated with cisplatin.

A potential biomarker for bipolar I disorder: serum arginine vasopressin levels

Objective: The neuropeptide arginine vasopressin (AVP) has effects on behavior and stress regulations which are impaired in bipolar disorder (BD). Only a very limited number of studies have investigated AVP levels in bipolar disorder in contrast to depressive disorders. The study aimed to investigate serum AVP levels during the manic, depressive, or remission periods and after treatment response in patients with bipolar I disorder (BD-I) and healthy controls. Methods: The study consisted of 67 patients with BD-I and 24 healthy controls. The patients were in the manic, depressive, or remission periods of BD-I. Serum AVP levels were assayed in the three groups of patients with BD-I and the controls at the study onset. Then, a second measurement of the AVP levels were carried out in the manic or depressive periods after treatment response. The treatment response was defined as a 50% decrease in the Young Mania Rating Scale and the Hamilton Depression Rating Scale scores for manic and depressive episodes, respectively. Results: The main finding was the significantly lower serum AVP levels in BD-I during manic, depressive, or remission periods compared to healthy controls. After-treatment-response serum AVP levels in depressive BD-I patients increased to the levels of healthy controls and became higher than in the remission period of BD-I. Conclusions: The global reduction in serum AVP levels may be an indicator of impaired neuronal function and neuroprogressive deterioration seen in BD. Notably, given the increased AVP levels in major depressive disorder, serum AVP levels may contribute to distinguishing depressive BD-I from major depressive disorder.

The effect of acetylsalicylic acid on vasopressin, serum insulin levels, insulin resistance, and biochemical parameters in rats induced with experimental diabetes type 2

Acetylsalicylic acid (ASA) treatment in diabetic patients is very important owing to the increasing hyperactivity of thrombocytes and atherosclerosis. In several investigations, it was reported that diabetes caused increased coronary artery disease, cerebrovascular disease, and death. In this study, we aimed to investigate the effect of ASA on osmoregulation, glycemic control, and some biochemical parameters in rats induced with experimental diabetes type 2. Twenty-four rats were randomly divided in four groups: control (I), ASA control (II), diabetic (III), and ASA diabetic (IV). Diabetes was induced by streptozotocin treatment (30 mg/kg, twice, intraperitoneal injection) in obese rats. ASA (150 mg/kg body weight, orally) was administered for 5 weeks in the ASA control and ASA diabetic groups. Serum electrolytes, creatinine, albumin, and total protein levels were analyzed with an autoanalyzer. Arginine vasopressin (AVP) and insulin were analyzed by ELISA techniques. At the end of the study ASA treatments had decreased the fasting blood glucose levels but had interestingly increased the serum AVP levels in diabetics rats. AVP levels were increased 2-fold by ASA treatment in diabetic rats. For the first time in this study, the hypoglycemic effect of ASA was attributed to an increase in blood volume by AVP levels. This explanation may be a new approach to the literature on this topic.

Brain Formaldehyde is Related to Water Intake behavior.

A promising strategy for the prevention of Alzheimer’s disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.

Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Syndrome of Inappropriate Secretion of Antidiuretic Hormone Found by Preoperative Electrolyte Analysis

To the Editor A 73-year-old woman, scheduled for extraction of 9 teeth under general anesthesia, had a serum sodium concentration of 137 mEq · L−1 at another hospital 3 weeks earlier. Preoperative blood analysis revealed a serum sodium concentration of 124 mEq · L−1, serum osmolality 260 mOsm · L−1, urinary sodium concentration 48 mEq · L−1 with a urinary osmolality of 822 mOsm · L−1, and serum arginine vasopressin concentration of 1.4 pg · mL−1 (normal range, 0.3–3.5 pg · mL−1). Thyroid and adrenal functions were normal. History included dementia, cerebral infarction, cerebellar atrophy, osteoporosis, lumbar and pelvic fractures, and chronic lymphocytic leukemia with anemia, and she had been bedridden in a hospital for several years. The medication history from the previous hospital disclosed that tablets of combined sulfamethoxazole and trimethoprim (Bactramin®) had been added because of the oral infection and a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with these drugs was suspected.1,2 Discontinuing these drugs, additional salt intake, fluid restriction, and infusion of hypertonic saline (3% NaCl) increased serum sodium concentration to 136 mEq · L−1 by the day before surgery.3,4 General anesthesia and surgery were uneventful and 6 days later, the patient was discharged from our hospital. The patient consented to publication of this report. Diagnosing SIADH based on clinical findings is difficult because of the lack of signs of excessive volume of extracellular fluid.2 In this case, SIADH was identified by chance based on preoperative electrolyte analysis. Drug-induced SIADH can occur with administration of vincristine, tricyclic antidepressants, opioids, antipsychotic drugs, carbamazepine, and selective serotonin reuptake inhibitors.2 To our knowledge, however, no reports have described SIADH induced by sulfamethoxazole and trimethoprim. If preoperative examination shows that hyponatremia is present preoperatively, additional measurements of serum osmolality, urinary sodium concentration, urinary osmolality, and serum arginine vasopressin level are warranted to clarify whether this finding is associated with SIADH. Kazuna Sugiyama, DDS, PhD Atsushi Kohjitani, DDS, PhD Yoko Iwase, DDS, PhD Yozo Manabe, DDS, PhD Department of Dental Anesthesiology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima, Japan [email protected]

The relationship between arginine vasopressin levels and hyponatremia following a percutaneous renal biopsy in children receiving hypotonic or isotonic intravenous fluids

Post-operative hyponatremia is a common complication in children which results from hypotonic fluid administration in the presence of arginine vasopressin (AVP) excess. We evaluated the relationship between the change in serum sodium and AVP levels following percutaneous renal biopsy in children receiving either hypotonic or isotonic fluids. This study was prompted after we encountered a patient who developed near-fatal hyponatremic encephalopathy following a renal biopsy while receiving hypotonic fluids. The relationship between the change in serum sodium and AVP levels was evaluated prior to (T0) and at 5 h (T5) following a percutaneous renal biopsy in 60 children receiving either hypotonic (0.6% NaCl, 90 mEq/L) or isotonic fluids (0.9% NaCl, 154 mEq/L). The proportion of patients with elevated AVP levels post-procedure was similar between those receiving 0.6 or 0.9% NaCl (30 vs. 26%). Patients receiving 0.6% NaCl with elevated AVP levels experienced a fall in serum sodium of 1.9 ± 1.5 mEq/L, whereas those receiving 0.9% NaCl had a rise in serum sodium of 0.85 ± 0.34 mEq/L with no patients developing hyponatremia. There were no significant changes in serum sodium levels in patients with normal AVP concentrations post-procedure in either group. In conclusion, elevated AVP levels were common among our patients following a percutaneous renal biopsy. Isotonic fluids prevented a fall in serum sodium and hyponatremia, while hypotonic fluids did not.

Effect of naloxone on somatostatin inhibition of arginine vasopressin response to physical exercise in normal men

To establish whether somatostatin (SRIH) and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, eight healthy men underwent four bicycle-ergometer tests until exhaustion: exercise control test; exercise plus SRIH, naloxone or SRIH plus naloxone. Serum AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During control test exercise significantly increased serum AVP levels, with a peak value 4.1 times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was significantly reduced by SRIH (AVP peak was only 2.8 times higher than baseline). When SRIH and naloxone were given together, the exercise-induced AVP rise was comparable to that observed in the control test. Results indicate a somatostatinergic involvement in the regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying SRIH inhibitory action, but not in mediation of the AVP response to physical exercise.

Serum level of arginine-vasopressin influences the prognosis of extensive-disease small-cell lung cancer

The purpose of this study is to elucidate the influence of serum arginine-vasopressin (AVP) level on prognosis of extensive-disease small-cell lung cancer (ED-SCLC). We retrospectively investigated the clinical records of 163 patients with ED-SCLC, who were admitted to Okayama University Hospital or National Shikoku Cancer Center Hospital. The influence of 14 pretreatment variables on survival was analyzed. In a multivariate analysis of 163 patients, elevation of serum LDH level (P = 0.028) and poor performance status (PS > or = 2, P = 0.002) were independent poor prognostic factors. In 34 patients whose serum AVP levels were available, high serum AVP level was related to the poor prognosis (P < 0.001). The serum-sodium level did not affect the survival. Median serum level of osmotic pressure in 34 patients was normal (284.9 mOsm/kg), although, serum osmotic pressure was low in four of six patients with high serum AVP level. In all patients with high serum AVP level, serum LDH level was elevated. The data from the current study suggested that serum LDH level and PS were the poor prognostic factors for ED-SCLC. But we additionally identified the prognostic significance of serum AVP level, which may be a more useful factor than serum-sodium level.

Increased urinary concentrating ability of P2Y2 receptor null mice is associated with marked increase in protein abundances of AQP2 and UT‐A in renal medulla

Agonist (ATP/UTP) activation of P2Y2 receptor (P2Y2-R) in the medullary collecting duct (mCD) decreases arginine vasopressin (AVP)-induced water flow, and releases PGE2, a potent inhibitor of AVP action on mCD. Hence, we analyzed age and sex matched P2Y2-R null (KO) and wild (WT) mice (N = 6/genotype; courtesy of Dr. Beverly Koller) after subjecting them to metabolic balance by feeding a gel diet containing fixed (70%) water content for 10 days. The water balance data obtained on the last three days were averaged. As compared to the WT mice the KO mice showed significantly less water consumption (− 11%; P < 0.04) and urine output (−32%; P < 0.02), and higher urinary osmolality (+ 38%; P < 0.002). There were no significant differences in total osmolar excretion or serum osmolality or AVP levels. Western analysis of renal medullas showed significant increases in mean protein abundances of AQP2 water channel (1.8-fold; P < 0.006), UT-A (~2-fold; P < 0.02), and a tendency for UT-B (+14%; P = 0.09) urea transporter isoforms. These data indicate that deletion of P2Y2-R apparently sensitizes mCD to the action of circulating AVP, resulting in direct increase in protein abundances of AQP2 and indirect increase in the UT-A, the key players in urinary concentration. Thus these findings underscore our hypothesis that in vivo P2Y2-R plays a significant role in modulating the mCD function.

Increased Water Intake Decreases Progression of Polycystic Kidney Disease in the PCK Rat

Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

Conivaptan: A selective vasopressin antagonist

Complex neurohormonal interactions dictate the body's volume status in different disease states. Besides the known pathologic activation of the renin-angiotensin-aldosterone axis and the effect of the adrenergic system, arginine vasopressin (AVP) represents a key element that is responsible for volume homeostasis. Serum AVP levels have been shown to be chronically elevated in different pathologic conditions that exhibit an imbalance in volume status, particularly in congestive heart failure. Evidently, elevated levels of AVP play an important role in the pathogenesis and progression of these diseases. AVP has many other receptor-mediated deleterious effects on vascular smooth muscles and cardiomyocytes. These effects are an integral part of the neurohormonal milieu in patients with heart failure. This assumption has propelled agents that antagonize the effects of vasopressin receptors to the forefront of clinical research, especially in heart failure management. This paper reviews current knowledge on conivaptan, a novel dual V1a/V2 vasopressin receptor antagonist.

Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy

Neurohumoral responses have been implicated in the pathogenesis of ischemia-evoked cerebral edema. In a well-characterized animal model of ischemic stroke, the present study was undertaken to 1) study the profile of plasma arginine-vasopressin (AVP), and 2) determine whether osmotherapy with mannitol and various concentrations of hypertonic saline (HS) solutions influence plasma AVP levels. Halothane-anesthetized adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion with the intraluminal filament technique. Plasma AVP levels (means +/- SD) were significantly elevated at 24 h (42 +/- 21 pg/ml), 48 h (50 +/- 28 pg/ml), and 72 h (110 +/- 47 pg/ml), and returned to baseline at 96 h (22 +/- 15 pg/ml) following middle cerebral artery occlusion compared with sham-operated controls (14 +/- 7 pg/ml). Plasma AVP levels at 72 h were significantly attenuated with 7.5% HS (37 +/- 8 pg/ml; 360 +/- 11 osmol/l) compared with 0.9% saline (73 +/- 6; 292 +/- 6 osmol/l), 3% HS (66 +/- 8 pg/ml; 303 +/- 12 osmol/l), or mannitol (74 +/- 9 pg/ml; 313 +/- 14 osmol/l) treatment. HS (7.5%) significantly attenuated water content in the ipsilateral and contralateral hemispheres compared with surgical shams, 0.9% saline, 3% HS, and mannitol treatments. Peak plasma AVP levels were not associated with direct histopathological injury to the anterior hypothalamus. Attenuation of brain water content with 7.5% HS treatment coincides with attenuated serum AVP levels, and we speculate that this may represent one additional mechanism by which osmotherapy attenuates edema associated with ischemic stroke.

Urinary aquaporin-2 levels in healthy volunteers.

Renal water handling is regulated by the release of arginine vasopressin (AVP) and the subsequent insertion of aquaporin 2 (AQP2) in the apical membrane of collecting duct cells. This in turn increases the membrane permeability to water and the passive reabsorption of water down the concentration gradient present in the medulla. Aquaporin 2 can be detected in the urine under conditions of antidiuresis. We wish to validate an assay for urinary AQP2. Fourteen volunteers participated in studies of water loading and water deprivation followed by the administration of 1-deamino-8-D-arginine vasopressin (dDAVP). Urine osmolality was measured by vapour pressure osmometry. Urinary AQP2 was measured by using a chemiluminescent assay. Baseline correlations between serum AVP levels, urinary osmolality and urinary AQP2 levels were not significant. Following the administration of dDAVP, a positive correlation between urine osmolality and urinary AQP2 was evident (r = 0.762). For specific conditions where renal water retention is stimulated via AVP, urinary AQP2 measurements provide a reproducible measurement of the renal actions of AVP.

Angiotensin II receptor pharmacology and AT1-receptor blockers.

Angiotensin II (Ang II) has diverse physiological actions leading, for example, to increases in extracellular volume, peripheral vascular resistance and blood pressure, and has also been implicated in the regulation of cell growth and differentiation. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors, designated as AT1 and AT2. Most effects of Ang II are mediated by AT1 receptors. Much less is known about the physiological role of AT2 receptors. Recent evidence suggests involvement of AT2 receptors in development, cell differentiation, apoptosis and regeneration in various tissues. AT1 and AT2 receptors have been shown to exert counteracting effects on cellular growth and differentiation, vascular tone and the release of arginine vasopressin (AVP). In each condition the AT2 receptor appears to down-modulate actions mediated by the AT1 receptor, resulting in decreased cellular proliferation, decreased levels of serum AVP levels or decreased vasoconstrictor responses. In addition, in neuronal cell lines, the AT2 receptor reportedly exerts antiproliferative effects and promotes neurite outgrowth, an effect accompanied by significant changes in the gene expression pattern of growth- and differentiation-related genes.

Management of vasodilatory shock after cardiac surgery: Identification of predisposing factors and use of a novel pressor agent

Background:Cardiopulmonary bypass can be associated with vasodilatory hypotension requiring pressor support. We have previously found arginine vasopressin to be a remarkably effective pressor in a variety of vasodilatory shock states. We investigated the incidence and clinical predictors of vasodilatory shock in a general population of cardiac surgical patients and the effects of low-dose arginine vasopressin as treatment of this syndrome in patients with heart failure. Methods: Patients undergoing cardiopulmonary bypass (n = 145) were studied prospectively. Preoperative ejection fraction, medications, and perioperative hemodynamics were recorded, and postbypass serum arginine vasopressin levels were measured. Vasodilatory shock was defined as a mean arterial pressure lower than 70 mm Hg, a cardiac index greater than 2.5 L/min/m 2, and norepinephrine dependence. Predictors of vasodilatory shock were investigated by logistic regression analysis. The hemodynamic responses of patients who received arginine vasopressin infusions for vasodilatory shock after cardiopulmonary bypass for left ventricular assist device placement or heart transplantation were analyzed retrospectively. Results: Eleven of 145 general cardiac surgery patients (8%) met criteria for postbypass vasodilatory shock. By multivariate analysis, an ejection fraction lower than 0.35 and angiotensin-converting enzyme inhibitor use were independent predictors of postbypass vasodilatory shock (relative risks of 9.1 and 11.9, respectively). Vasodilatory shock was associated with inappropriately low serum arginine vasopressin concentrations (12.0 ± 6.6 pg/mL). Retrospective analysis found 40 patients with postbypass vasodilatory shock who received low-dose arginine vasopressin infusions, resulting in increased mean arterial pressure and decreased norepinephrine requirements. Conclusions: Low ejection fraction and angiotensin-converting enzyme inhibitor use are risk factors for postbypass vasodilatory shock, and this syndrome is associated with vasopressin deficiency. In patients exhibiting this syndrome after high-risk cardiac operations, replacement of arginine vasopressin increases blood pressure and reduces catecholamine pressor requirements. (J Thorac Cardiovasc Surg 1998;116:973-80)