Reduction In Urine Volume Research Articles

A case of idiopathic diabetes insipidus presented with bilateral hydroureteronephrosis and neurogenic bladder: A pediatric case report and literature review

Diabetes insipidus (DI) is a condition with heterogeneous clinical symptoms characterized by polyuria (urine output >4 mL/kg/hr) and polydipsia (water intake >2 L/m (2)/d). In children, acquired nephrogenic DI (NDI) is more common than central DI (CDI). Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. A water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI from CDI and diagnose their incomplete forms. Neonates and young infants are better managed with hydration therapy alone. Older children with CDI are treated with desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP). Its oral form is safe, highly effective and has dosing flexibility. We report a case of an 8-year-old male patient with CDI with severe bilateral non-obstructive hydronephrosis and megaureter. Dramatic clinical and radiological responses to dDAVP treatment were achieved and therapy reduced urine volume and led to marked radiological improvement in hydronephrosis.

Kidney stone risk following Roux-en-Y gastric bypass surgery.

Since the first report in 2005, Roux-en-Y gastric bypass (RYGB) surgery has been linked to a variety of metabolic changes that alter kidney stone risk. The studies with the highest level of evidence, performed in non-stone forming patients before and after RYGB, cite a number of kidney stone risk factors, including a 25% increase in urinary oxalate, a 30% decrease in urinary citrate, and reduction in urine volume by half a liter. In addition to these, recent clinical and experimental studies have contributed to our understanding of the pathophysiology of stone disease in this unique population. This review summarizes the current RYGB urinary chemistry profiles and epidemiological studies, outlines known and theoretical mechanisms of hyperoxaluria and hypocitrituria, and provides some standard recommendations for reducing stone risk in RYGB stone formers as well as some novel ones, including correction of metabolic acidosis and use of probiotics.

Mechanisms Contributing to Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated with Bardoxolone Methyl

Background: Bardoxolone methyl, an Nrf2-activating and nuclear factor-κB-inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase 3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD). The trial was terminated because of an increase in heart failure events in the bardoxolone methyl group, many of which appeared related to fluid retention. Thus, additional analyses were conducted to explain these serious adverse events. Methods: Patients (n = 2,185) were randomized to receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine collections were analyzed in a subset of the BEACON population and from a separate, open-label pharmacology study in patients with stage 3b/4 CKD and T2DM administered 20 mg bardoxolone methyl once daily for 56 consecutive days. Results: Bardoxolone-methyl-treated patients in the BEACON substudy had a clinically meaningful reduction in urine volume and sodium excretion at week 4 relative to baseline (p < 0.05), and a separate study revealed that decreased sodium excretion and urine output occurred in some patients with stage 4 CKD but not those with stage 3b CKD. The clinical phenotype of fluid overload and heart failure in BEACON was similar to that observed with endothelin receptor antagonists in advanced CKD patients, and preclinical data demonstrate that bardoxolone methyl modifies endothelin signaling. Conclusions: The totality of the evidence suggests that through modulation of the endothelin pathway, bardoxolone methyl may pharmacologically promote acute sodium and volume retention and increase blood pressure in patients with more advanced CKD.

Codeine-Induced Syndrome of Inappropriate Antidiuretic Hormone: Case Report

The syndrome of inappropriate antidiuretic hormone was first described in 1957 by Schwartz, and is characterised by hyponatraemia, inappropriately increased urine osmolality and urine sodium, and decreased serum osmolality in a euvolemic patient without edema. A patient with the syndrome of inappropriate antidiuretic hormone should have normal cardiac, renal, adrenal, hepatic, and thyroid functions and should not take any diuretics. We present a case of the syndrome of inappropriate antidiuretic hormone caused by codeine and associated with reduced urine volume, increased urine sodium, and decreased serum sodium concentration. The syndrome of inappropriate antidiuretic hormone is a disease that can lead to morbidity and even mortality. Clinicians should measure serum electrolytes intermittently in order to avoid missing the diagnosis of the syndrome of inappropriate antidiuretic hormone in patients using opioid.

Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter

Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI). Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in Li-NDI. The paradoxical antidiuretic action of HCTZ in Li-NDI is generally attributed to increased sodium and water uptake in proximal tubules as a compensation for increased volume loss due to HCTZ inhibition of the Na-Cl cotransporter (NCC), but alternative actions for HCTZ have been suggested. Here, we investigated whether HCTZ exerted an NCC-independent effect in Li-NDI. In polarized mouse cortical collecting duct (mpkCCD) cells, HCTZ treatment attenuated the Li-induced downregulation of aquaporin-2 (AQP2) water channel abundance. In these cells, amiloride reduces cellular Li influx through the epithelial sodium channel (ENaC). HCTZ also reduced Li influx, but to a lower extent. HCTZ increased AQP2 abundance on top of that of amiloride and did not affect the ENaC-mediated transcellular voltage. MpkCCD cells did not express NCC mRNA or protein. These data indicated that in mpkCCD cells, HCTZ attenuated lithium-induced downregulation of AQP2 independently of NCC and ENaC. Treatment of Li-NDI NCC knockout mice with HCTZ revealed a significantly reduced urine volume, unchanged urine osmolality, and increased cortical AQP2 abundance compared with Li-treated NCC knockout mice. HCTZ treatment further resulted in reduced blood Li levels, creatinine clearance, and alkalinized urinary pH. Our in vitro and in vivo data indicate that part of the antidiuretic effect of HCTZ in Li-NDI is NCC independent and may involve a tubuloglomerular feedback response-mediated reduction in glomerular filtration rate due to proximal tubular carbonic anhydrase inhibition.

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

Despite several decades of research, there is still uncertainty regarding the optimal lithium dosage regimen associated with a decreased risk of renal effects, such as polyuria, in patients with bipolar affective disorder. We present an updated review of the literature to provide an informed dosing regimen recommendation for prescribers. Major databases MEDLINE and Embase were searched using terms, such as lithium, drug administration schedule, dose-response relationship, once daily, twice daily, and sustained release. In addition, the bibliographies of related publications were manually searched. A total of 20 trials were included. Some trials showed a reduction in urine volume with single daily dosing (SDD), while others showed no change. The only trial evaluating patients newly started on lithium found a reduction in urinary frequency with SDD after 21 days. Trials examining renal biopsy results found that multiple daily doses were associated with more pathologic damage to the kidneys. SDD regimens were generally well tolerated, and no reduction in efficacy was noted in any of the trials. The available evidence is contradictory as to whether SDD of lithium reduces polyuria; however, no trial has demonstrated any downfall of SDD in terms of prophylactic efficacy or adverse effects. Given the added benefits of SDD, such as improved compliance, we recommend patients newly started on lithium should be converted to a SDD of lithium at bedtime once an appropriate daily dose is determined.

Urocortin-2 Infusion in Acute Decompensated Heart Failure: Findings From the UNICORN Study (Urocortin-2 in the Treatment of Acute Heart Failure as an Adjunct Over Conventional Therapy)

The purpose of this study is to investigate the effects of urocortin-2 as adjunct therapy in acute decompensated heart failure (ADHF). Urocortin-2 produced favorable integrated effects in experimental heart failure but there are no equivalent human data. We describe the first therapeutic study of urocortin-2 infusion in ADHF. Fifty-three patients with ADHF were randomly assigned to 5 ng/kg/min of urocortin-2 or placebo infusion for 4 h as an adjunct therapy. Changes in vital signs, plasma neurohormonal and renal indices during treatment were compared using repeated-measures analysis of covariance. Ten patients in each arm underwent more detailed invasive hemodynamic evaluation. Urocortin-2 produced greater falls in systolic blood pressure compared to placebo (16 ± 5.8 mm Hg, p < 0.001) with nonsignificant increases in heart rate (5.7 ± 3.8 beats/min, p = 0.07) and increased cardiac output (2.1 ± 0.4 l/min vs. -0.1 ± 0.4 l/min, p < 0.001) associated with a 47% reduction in calculated total peripheral resistance (p = 0.015). Falls in pulmonary artery and pulmonary capillary wedge pressures did not differ significantly between groups. Urocortin-2 reduced urine volume and creatinine clearance during infusion but these returned to above baseline level in the 8 h after infusion. Plasma renin activity rose briefly with urocortin-2 coinciding with reductions in blood pressure (p < 0.001). B-type natriuretic peptide levels fell significantly over 24 h with urocortin-2 (p < 0.01) but not with placebo. Urocortin-2 infusion in ADHF markedly augmented cardiac output without significant reflex tachycardia. Renal indices fell transiently concurrent with urocortin-2-induced reductions in blood pressure. Further investigations are required to uncover the full potential of urocortin-2 in treating ADHF.

Calcium oxalate supersaturation increases early after Roux-en-Y gastric bypass

BackgroundCalcium oxalate (CaOx) nephrolithiasis is an adverse effect of Roux-en-Y gastric bypass surgery (RYGB). It is unknown when the increased risk for CaOx stone formation occurs after surgery. MethodsWe studied 13 morbidly obese adults undergoing RYGB with 24-hour urine collections at 4 weeks before and 1, 2, 4, and 6 months after surgery and computed CaOx relative saturation ratio (RSR) by EQUIL2. ResultsEleven patients were female, mean±standard deviation age was 41.1±7.2 years, and none had diabetes or chronic kidney disease. Median (interquartile range) urinary oxalate excretion increased linearly from 12.6 (10.9–37.9) mg/24 hr at baseline to 28.4 (14.4–44.0) mg/24 hr at 6 months (slope = .188; P = .005). CaOx RSR increased significantly at 2 months after RYGB (1.4 [1.2–2.4] to 4.9 [1.7–10.0]; P = .017) and rose throughout the study to 5.7 (3.7–12.2) at 6 months (P = .001) with a positive linear slope (.255; P = .001). One patient had critical CaOx supersaturation (RSR = 34.7) and severe hyperoxaluria (101.7 mg/24 hr) at 6 months after RYGB. Significant decreases over time were seen in urine volume and sodium and potassium excretion, but no changes were noted in urinary pH, calcium, magnesium, or citrate. ConclusionsOur data suggest that CaOx RSR, and thus risk for nephrolithiasis, rises as early as 2 months after RYGB and increases gradually in the first 6 months, largely because of reduced urine volume and increased urinary oxalate excretion. Interventions to reduce CaOx RSR, such as adequate fluid intake and agents to bind enteric oxalate, need to be evaluated in patients at risk for nephrolithiasis after RYGB.

Shaking stress aggravates burn-induced cardiovascular and renal disturbances in a rabbit model

The aim of this study was to address the effects of shaking stress (a.k.a. physical agitation) on burn-induced remote organ injury and to evaluate the application of delayed fluid resuscitation to treat severe burns under shaking conditions. Healthy adult male rabbits, weighing 2.50±0.40kg, were randomly assigned to the following groups: control group, burn group, and burn+shaking group. One half of burned animals received a 6-h delayed fluid resuscitation and the other half remained untreated. Cardiovascular hemodynamics and functional and pathological changes of the heart and kidney were examined. Compared to normal controls, untreated burned animals showed decreased hemodynamic parameters, increased serum lactic acid, and severe myocardial inflammation. The burn-induced hemodynamic abnormalities and cardiac injury were aggravated by shaking stress. Burn injury led to reduced urine volume, elevated serum creatinine and blood urea nitrogen, and formation of erythrocyte casts in renal tubules. Shaking stimulation worsened the burn-associated functional and pathological changes of the kidney. Fluid resuscitation markedly mitigated cardiac and renal injury in burned animals, and, to a lesser extent, in the presence of shaking stimulation. Shaking stimulation aggravates burn-induced cardiovascular and renal disturbances. Delayed fluid resuscitation attenuates cardiac and renal damages in burn injury under shaking conditions.

Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia

Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia

MPGES-1 deletion potentiates urine concentrating capability after water deprivation

PGE(2) plays an important role in the regulation of fluid metabolism chiefly via antagonizing vasopressin-induced osmotic permeability in the distal nephron, but its enzymatic sources remain uncertain. The present study was undertaken to investigate the potential role of microsomal PGE synthase (mPGES)-1 in the regulation of urine concentrating ability after water deprivation (WD). Following 24-h WD, wild-type (WT) mice exhibited a significant reduction in urine volume, accompanied by a significant elevation in urine osmolality compared with control groups. In contrast, in response to WD, mPGES-1 knockout (KO) mice had much less urine volume and higher urine osmolality. Analysis of plasma volume by measurement of hematocrit and by using a nanoparticle-based method consistently demonstrated that dehydrated WT mice were volume depleted, which was significantly improved in the KO mice. WD induced a twofold increase in urinary PGE(2) output in WT mice, which was completely blocked by mPGES-1 deletion. At baseline, the KO mice had a 20% increase in V(2) receptor mRNA expression in the renal medulla but not the cortex compared with WT controls; the expression was unaffected by WD irrespective of the genotype. In response to WD, renal medullary aquaporin-2 (AQP2) mRNA exhibited a 60% increase in WT mice, and this increase was greater in the KO mice. Immunoblotting demonstrated increased renal medullary AQP2 protein abundance in both genotypes following WD, with a greater increase in the KO mice. Similar results were obtained by using immunohistochemistry. Paradoxically, plasma AVP response to WD seen in WT mice was absent in the KO mice. Taken together, these results suggest that mPGES-1-derived PGE(2) reduces urine concentrating ability through suppression of renal medullary expression of V(2) receptors and AQP2 but may enhance it by mediating the central AVP response.

Phloridzin reduces blood glucose levels and improves lipids metabolism in streptozotocin-induced diabetic rats

Phloridzin is the specific and competitive inhibition of sodium/glucose cotransporters in the intestine (SGLT1) and kidney (SGLT2). This property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. Phloridzin is one of the dihydrochalcones typically contained in apples and in apple-derived products. The effect of phloridzin orally doses 5, 10, 20 and 40mg/kg body weight on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1. From beneficial effect of this compound is significant reduction of blood glucose levels and improve dyslipidemia in diabetic rats. As a well-known consequence of becoming diabetic, urine volume and water intake were significantly increased. Administration of phloridzin reduced urine volume and water intake in a dose-dependent manner. Phloretin decreases of food consumption, as well as a marked lowering in the weight. In conclusion, this compound could be proposed as an antihyperglycemic and antihyperlipidemic agent in diabetes and potential therapeutic in obesity.

Management of a hemophilia patient in renal replacement therapy

AbstractWe describe the case of a male hypertensive patient with severe hemophilia A. In August 1999 he was admitted to our nephrology department, with hemarthrosis, severe hypertension, dyspnea with minimal efforts, increasing blood urea nitrogen, anemia, uremic symptoms, reduced urine volume, mild edema of the lower limbs, and no hyperkalemia. Imaging confirmed the diagnosis of end‐stage renal disease. A Tenckhoff peritoneal dialysis catheter was inserted, and he began continuous ambulatory peritoneal dialysis. In August 2005 he evolved to peritoneal failure (peritoneal equilibration test showing ultrafiltration disorder I) and was transferred to hemodialysis. A permanent catheter was inserted into the right subclavian vein. Hemodialysis sessions lasted 4 hours, three times a week, and gradually resulted in hemodynamic stabilization. In September 2005, an arteriovenous fistula was placed in the right forearm between the cephalic vein and the radial artery. In January 2007 the patient was admitted with abdominal and epigastric pain, double‐lumen catheter infection, peritoneal catheter infection, globoid tympanic abdomen, and mild pain on palpation. Preliminary studies showed a large preperitoneal hematoma with bowel compression. Due to the catheter infection, we decided to puncture the fistula using a 17‐G needle. Apart from some bleeding during and after the beginning of hemodialysis, there were no other fistula complications. The patient had progressive worsening of clinical symptoms and died in February 2007. In summary, an individualized treatment plan, mainly adequate hemostatic monitoring, care of the dialysis access, and multiprofessional and family involvement, may help in the management of hemophilia patients undergoing dialysis. Dial. Transplant. © 2011 Wiley Periodicals, Inc.

Angiotensin II Receptor Blocker, Losartan, Ameliorates Gentamicin-Induced Oxidative Stress and Nephrotoxicity in Rats

Background/Aims: This study investigates the ameliorative effect of concurrent and pretreatment with angiotensin II receptor blocker, losartan (LOS), against gentamicin (GEN)-induced renal damage. Methods: Rats were divided into five groups: control, LOS group (10 mg/kg/day for 7 days), GEN group (100 mg/kg/day for 7 days), GEN + LOS pretreated group (treated with LOS for 7 days followed by 7 days of GEN), and GEN + LOS concurrently treated group (simultaneously treated with GEN and LOS for 7 days). Results: Concurrent treatment with LOS significantly reduced urine volume, microalbuminuria, blood urea nitrogen (BUN) and serum creatinine levels elevated by GEN administration. Also, LOS significantly attenuated GEN-induced increase in malondialdehyde and decrease in reduced glutathione, and catalase and superoxide dismutase activities in renal cortical homogenates. Additionally, histopathological examination and scoring showed that LOS markedly ameliorated GEN-induced renal tubular damage. Conversely, pretreatment with LOS produced no significant changes in urine volume, microalbuminuria, BUN and serum creatinine with little changes in the oxidative stress parameters when compared with the GEN-treated group. Conclusion: Concurrent treatment with LOS has produced marked amelioration in biochemical indices and oxidative stress parameters against GEN-induced nephrotoxicity. Accordingly, LOS can be considered a feasible antihypertensive drug for hypertensive patients simultaneously treated with GEN.

Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease

The present study investigated the prevalence of infection by JC and BK polyomaviruses (JCV and BKV) in patients with chronic renal disease (CRD), kidney transplant recipients, and a control group of asymptomatic subjects. We tested a total of 295 urine samples. After DNA extraction, polymerase chain reaction assay was used to amplify a fragment of 173 bp of the polyomavirus T antigen, followed by analysis using the BamHI restriction endonuclease. Infection by polyomavirus was detected in 17.6% (52/295 subjects) of the subjects. Whereas 30.5% (18/59) of transplant recipients were infected, the frequency was only 22.4% (30/134) in the control subjects, and 3.9% (4/102) in the CRD group (all JCV). The vast majority of infections (88.9%; 16/18) in transplant recipients were of the BKV type, whereas this type was absent in CRD patients, and made up only 10.0% (3/30) of infections in the control group. The risk of BKV infection was 72 times greater in renal transplant patients than in asymptomatic subjects. The low frequency of infection found in CRD patients may have been related to elevated levels of urea excreted in the urine, together with reduced urine volume and cell content. These factors may combine to reduce viral load or inhibit amplification. The results of the study indicate a need for the routine screening for polyomavirus in pre- and post-transplant patients, as well as organ donors, considering that BKV infection has been associated with graft rejection in kidney transplants.

A new liquid chromatography/mass spectrometry method for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL) in urine

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic nitrosamine produced upon curing tobacco. It is present in tobacco smoke and undergoes metabolism to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in the lungs. NNAL undergoes further uridine diphosphate glucuronosyltransferase (UGT)-mediated metabolism to give N- and O-glucuronide metabolites, which together with free (non-conjugated) NNAL are then excreted in the urine. The ability to conduct validated analyses of free and conjugated NNAL in human urine is important in order to assess inter-individual differences in lung cancer risk from exposure to cigarette smoke. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography/multiple reaction monitoring/mass spectrometry (LC/MRM-MS) provides the highest bioanalytical specificity possible for such analyses. We describe a novel derivatization procedure, which results in the formation of a pre-ionized N-propyl-NNAL derivative. The increased LC/MS sensitivity arising from this derivative then makes it possible to analyze free NNAL in only 0.25 mL urine. This substantial reduction in urine volume when compared with other methods that have been developed will help preserve the limited amounts of stored urine samples that are available from on-going longitudinal biomarker studies. The new high sensitivity SID LC/MRM-MS assay was employed to determine free and conjugated NNAL concentrations in urine samples from 60 individual disease-free smokers. Effects of inter-individual differences in urinary creatinine clearance on NNAL concentrations were then assessed and three metabolizer phenotypes were identified in the 60 subjects from the ratio of urinary NNAL glucuronides/free NNAL. Poor metabolizers (PMs, 14 subjects) with a ratio of NNAL glucuronides/free NNAL <2 (mean = 1.3), intermediate metabolizers (IMs, 36 subjects) with a ratio between 2 and 5 (mean = 3.4), and extensive metabolizers (EMs, 10 subjects) with a ratio >5 (mean = 11.1).

Nocturnal enuresis—investigating the possible role of water transfer across the urothelium by looking for the presence of vasopressin receptors and aquaporins in urothelium

Aims To test the hypothesis that vasopressin-sensitive aquaporin 2 (AQP2) may be present in the human urothelium and contribute towards obtaining night time continence. Background In studies comparing dry and wet nights in children with enuresis it was hypothesised that there may be water transfer across the urothelium overnight resulting in an increase in urine concentration and a reduction in urine volume. The authors postulated that human urothelium would have to express the vasopressin receptor and AQP2. Methods Using previously evaluated techniques, human urothelium was isolated and used to prepare messenger RNA, perform immunohistological studies and to establish finite NHU cell lines. All samples were then studied for expression of vasopressin receptor and aquaporins 0–12. Results Native and cultured urothelia were negative for vasopressin receptor and AQP2 transcripts, whereas transcripts for aquaporins 3, 4, 7, 9 and 11 were detected. Immunohistochemistry revealed human urothelium to be intensely positive for AQP3 in the basal and intermediate layers of the urothelium, localising to intercellular borders. AQP 4 and 7 showed less intense cytoplasmic expression throughout the urothelium. No immunoreactivity was found for AQP 9. Conclusion The original hypothesis that water transfer might occur across human urothelium due to the presence of vasopressin-sensitive AQP2 is incorrect. The detection of AQP 3 and 4 raises the possibility that water and urea transfer may occur across the urothelium. However, it is yet to be determined whether these proteins contribute to urinary continence mechanisms.

16 IDENTIFICATION OF THE HENLE'S LOOP AS A MAJOR SITE OF SODIUM RETENTION IN EXPERIMENTAL PREASCITIC CIRRHOSIS: EFFECTS OF PARATHYROID HORMONE

Extracellular Ca stimulates membrane-bound calcium-sensing receptors (CaRs). In turn, CaRs stimulation leads to PGE2-mediated decrease in protein content of Na-K-2Cl co-transporters (BSC-1) in the thick ascending limb (TAL) of Henle’s loop and of aquaporin 2 (AQP2) water channels in collecting ducts. Parathyroid hormone (PTH) increases CaRs expression and, consequently, decreases BSC-1 and AQP2 content. To assess this Ca-dependent diuretic system in preascitic cirrhosis we evaluated renal function, hormonal status, PGE2 urinary excretion, renal content of BSC-1 and CaRs in three groups of rats: one group of controls receiving s.c. 5% glucose solution and two groups of rats with CCl4-induced preascitic cirrhosis receiving either glucose solution or five s.c. doses of 10 mcg/kg PTH (one dose every 12h) prior to study. The amount of fluid administered to each group was the same. Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (P < 0.05); western blot analysis revealed reduced CaRs and increased BSC-1 protein content in cirrhotic rat kidneys (all P < 0.01). PTH-treated cirrhotic rats had urine and sodium excretion normalized; s.c. PTH increased also renal plasma flow, PGE2 urinary excretion, free-water clearance, reduced BSC-1 and augmented CaRs content in cirrhotic rat kidneys (all P < 0.01 v. untreated cirrhosis). In conclusion, in preascitic cirrhosis sodium retention is linked to downregulation of renal CaRs and upregulation of tubular Na-K-2Cl co-transporters. PTH returns these biomolecular alterations and sodium and urine excretions to normality. Therefore, exaggerated sodium reabsorption in Henle’s loop is largely responsible for sodium retention in preascitic cirrhosis.

Stimulus‐Specific Neuroendocrine Responses to Osmotic Challenges in Apelin Receptor Knockout Mice

The expression of the novel peptide apelin and its receptor APJ within specific regions of the brain, in particular the magnocellular neurones of the hypothalamus and the circumventricular organs, has implicated the apelinergic system in mechanisms controlling fluid homeostasis. In addition, apelin and APJ are considered to be involved in controlling arginine vasopressin (AVP) secretion into the circulation and release within the hypothalamic-neurohypophysial system. To clarify the role of APJ during regulation of fluid homeostasis, we compared the effects of osmotic stimulation on the urinary concentrating capacities and central nervous system responses of salt-loaded (SL) and water-deprived (WD) female APJ knockout (APJ(-/-)) mice and wild-type controls. SL resulted in a significantly increased urine volume in APJ(-/-) mice compared to wild-type controls, whereas WD in APJ(-/-) mice failed to reduce urine volume as seen in wild-type controls. AVP transcripts in the supraoptic and paraventricular nuclei and plasma AVP concentrations were significantly attenuated in SL APJ(-/-) mice compared to SL wild-type, but increased comparably in wild-type and APJ(-/-) mice after WD. Analysis of c-fos mRNA expression in the median preoptic nucleus and subfornical organ in response to either WD or SL showed attenuated expression in APJ(-/-) compared to wild-type mice. These findings further implicate the apelinergic system in mechanisms controlling fluid homeostasis, particularly at a neuroendocrine level, and suggest stimulus-specific involvement in vasopressinergic activity.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

BackgroundNitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of Nω-nitro-L-arginine methyl ester (L-NAME, 40 μg), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO.ResultsInjections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II.Discussion and conclusionThus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.