Urine Volume Rate Research Articles

Excitatory purinergic and cholinergic expression changed in a partial bladder outlet obstruction-induced overactive bladder rat model

Overactive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin–eosin (H&E) and Masson’s trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression.

Post-Operative Kidney Function Using Deep Hypothermic Circulatory Arrest (DHCA) in Aortic Arch Operation.

BackgroundAlthough deep hypothermic circulatory arrest (DHCA) is a useful option to protect the central nervous system during aortic arch operations, the influence of simultaneous renal ischemia remains controversial.Patients and MethodsThis is a retrospective observational study. Sixty-three patients who underwent thoracic aortic surgery with DHCA and 24 patients who underwent cardiac surgery without DHCA were included in this study. The mean age, preoperative serum creatinine (Cr) level, preoperative estimated glomerular filtration rate (eGFR), peak serum Cr level up to 48 hrs post-operative, elevation rate of Cr compared to the preoperative serum Cr, urine volume rate up to 48 hrs post-operative and AKI staging using the KDIGO criteria were estimated for each patient. Clinical parameters for 3 months after the operation and the 3-month post-operative mortality rate were assessed. Mean values indicating kidney function or distribution of the AKI stages were compared between patients with and without DHCA. Patients with DHCA were further divided according to the duration of ischemia to compare the values for the kidney function of each group, distribution of AKI stages and mortality.ResultsThe parameters indicating AKI of the patients with DHCA were significantly more severe than those without DHCA. Patients who had undergone an ischemic state for more than 40 min revealed significantly higher peak serum Cr, elevation rate of serum Cr, less urine volume up to 48 hrs post-operative compared with those without DHCA. Distribution of the AKI stages was related to the duration of ischemia. The 3-month post-operative mortality of the patients with DHCA was significantly higher than those without DHCA.LimitationsThis study had limitations such as its retrospective design and small number patients, and the data will be required confirmation with other prospective studies.ConclusionDHCA is closely related to AKI up to 48 hrs post-operative and death during the 3 months following surgery.

Pyrrosia petiolosa Extract Ameliorates Ethylene Glycol-Induced Urolithiasis in Rats by Inhibiting Oxidative Stress and Inflammatory Response

Objective To study the therapeutic effect and mechanism of Pyrrosia petiolosa (P. petiolosa) extract on ethylene glycol- (EG-) induced urolithiasis in rats. Methods Thirty SD male rats were randomly divided into five groups (n = 6): control group, EG group, and P. petiolosa group (25 mg/kg, 50 mg/kg group, and 100 mg/kg). Biochemical testing was adopted for measuring the blood and urine parameters, as well as the level of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde acid (MDA) in kidney tissues. HE staining and ELISA were utilized to observe the histopathological changes and detect the level of IL-1β, IL-6, MCP-1, and TNF-α in the kidney tissue, respectively. And western blot was performed for checking NOX2, NOX4, TGF-β1, p-Smad3, Smad3, p-Smad2, and Smad2 protein expression level in kidney tissues. Results EG could significantly increase the level of blood urea nitrogen, creatinine, and Na in serum and 24-hour urinary protein, oxalate, uric acid, creatinine, calcium, and phosphorus in urine and decreased the urine volume in rats. Whereas P. petiolosa extract was able to greatly decrease the level of related parameters in serum and urine in a dose-dependent manner, but did not affect the urine pH. In addition, P. petiolosa extract notably ameliorated EG-induced renal tissue injury. Compared with the EG group, P. petiolosa extract markedly raised the level of SOD and GSH and decreased the MDA level and the expression of NOX2 and NOX4 in the kidney tissue. Moreover, P. petiolosa extract also lowered the level of IL-1β, IL-6, MCP-1, and TNF-α in EG-stimulated kidney tissue and inhibited the protein level of EG-induced TGF-β1, p-Smad3, and p-Smad2 in a concentration-dependent manner. Conclusion P. petiolosa extract can improve EG-induced urolithiasis in rats by inhibiting oxidative stress, inflammatory response, and the activation of TGF-β pathway.

Decreased renal function increases the nighttime urine volume rate by carryover of salt excretion to the nighttime

To determine the pathophysiology of nocturnal polyuria associated with renal dysfunction, patients who underwent laparoscopic nephrectomy were prospectively studied. The diurnal variation in urine volume, osmolality, and salt excretion were measured on preoperative day 2 and postoperative day 7. The factors associated with an increase in the nighttime urine volume rate with decreased renal function were evaluated using multiple linear regression analysis. Forty-nine patients were included. The estimated glomerular filtration rate decreased from 73.3 ± 2.0 to 47.2 ± 1.6 mL/min/1.73 m2 (P < 0.01) and the nighttime urine volume rate increased from 40.6% ± 2.0% to 45.3% ± 1.5% (P = 0.04) with nephrectomy. The nighttime urine osmolality decreased from 273 ± 15 to 212 ± 10 mOsm/kg and the nighttime salt excretion rate increased from 38.7% ± 2.1% to 48.8% ± 1.7% (both P < 0.01) with nephrectomy. Multiple linear regression analysis showed that the increase in the nighttime urine volume rate was strongly affected by the increase in the nighttime salt excretion rate. A decrease in renal function causes an increase in the nighttime urine volume rate, mainly because of an increase in nighttime salt excretion.Trial registration number: UMIN000036760 (University Hospital Medical Information Network Clinical Trials Registry).Date of registration: From 1 June 2019 to 31 October 2020.

Protective Mechanism of Xiyin Liangxue Decoction on Immunoglobulin A Nephropathy Rats

Immunoglobulin A nephropathy is the most common glomerular disease in China, accounting for about 20 % to 47 % of primary glomerular diseases. Xiyin liangxue decoction is a common experience in the treatment of Immunoglobulin A nephropathy in recent years. The research of this formula in the clinical treatment of Immunoglobulin A nephropathy has achieved obvious curative effect. This article aims to study the protective mechanism of xiyin liangxue decoction on Immunoglobulin A nephropathy rats and analyzes and compares the advantages of xiyin liangxue decoction and western medicine in the treatment of Immunoglobulin A nephropathy rats with Sprague dawley nephropathy rats. The results of the study showed that after treatment of Immunoglobulin A nephropathy rats with xiyin liangxue decoction, the renal function of the rats in the treatment group was significantly improved, the expressions of alanine aminotransferase and aspartate aminotransferase increased by 19 % and 5 % and the expressions of albumin and globulin increased by 19 % and 25 %. In addition, in the treatment group, the number of urine red blood cells, urine protein and urine mannose binding lectin decreased by 29 %, 13 % and 25 %, respectively. The urine volume of rats in the high dose group was significantly reduced by 13 % and the expressions of blood urea nitrogen and blood creatinine increased 22 % and 8 % respectively. After treatment with xiyin liangxue decoction, the cure rate of experimental Immunoglobulin A rats reached 24 % and 33 % had significant improvement. It can be seen that xiyin liangxue decoction has a good clinical treatment effect on Immunoglobulin A nephropathy rats.

Discovery and in vivo effects of novel human natriuretic peptide receptor A (NPR-A) agonists with improved activity for rat NPR-A

Natriuretic peptide receptor A (NPR-A) agonists were evaluated in vivo by optimizing the structure of quinazoline derivatives to improve agonistic activity for rat NPR-A. A 1,4-Cis-aminocyclohexylurea moiety at 4-position and hydroxy group of d-alaninol at 2-position on the quinazoline ring were found to be important factors in improving rat NPR-A activity. We identified potent quinazoline and pyrido[2,3-d]pyrimidine derivatives against rat NPR-A, with double-digit nanomolar EC50 values. The in vivo results showed that compound 56b administered at 1.0 mg/kg/min significantly increased plasma cGMP concentration and urine volume in rats. We discovered novel potent NPR-A agonists that showed agonistic effects similar to those of atrial natriuretic peptide.

The EP3 receptor regulates water excretion in response to high salt intake

The mechanisms by which prostanoids contribute to the maintenance of whole body water homeostasis are complex and not fully understood. The present study demonstrates that an EP3-dependent feedback mechanism contributes to the regulation of water homeostasis under high-salt conditions. Rats on a normal diet and tap water were placed in metabolic cages and given either sulprostone (20 μg·kg-1·day-1) or vehicle for 3 days to activate EP3 receptors in the thick ascending limb (TAL). Treatment was continued for another 3 days in rats given either 1% NaCl in the drinking water or tap water. Sulprostone decreased expression of cyclooxygenase 2 (COX-2) expression by ∼75% in TAL tubules from rats given 1% NaCl concomitant with a ∼60% inhibition of COX-2-dependent PGE2 levels in the kidney. Urine volume increased after ingestion of 1% NaCl but was reduced ∼40% by sulprostone. In contrast, the highly selective EP3 receptor antagonist L-798106 (100 μg·kg-1·day-1), which increased COX-2 expression and renal PGE2 production, increased urine volume in rats given 1% NaCl. Sulprostone increased expression of aquaporin-2 (AQP2) in the inner medullary collecting duct plasma membrane in association with an increase in phosphorylation at Ser269 and decrease in Ser261 phosphorylation; antagonism of EP3 with L-798106 reduced AQP2 expression. Thus, although acute activation of EP3 by PGE2 in the TAL and collecting duct inhibits the Na-K-2Cl cotransporter and AQP2 activity, respectively, chronic activation of EP3 in vivo limits the extent of COX-2-derived PGE2 synthesis, thereby mitigating the inhibitory effects of PGE2 on these transporters and decreasing urine volume.

Effect of Zhuangyao Jianshen Wan(ZYJCW)on P2X1 and P2X3 mRNA expressions in rats with diuresis caused by kidney deficiency

To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.

Polyphenol-rich extract of Vernonia amygdalina (Del.) leaves ameliorated cadmium-induced alterations in feeding pattern and urine volume of male Wistar rats.

Aim:To determine the effects of a polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) on the feeding pattern of rats that are exposed to cadmium (Cd) toxicity.Materials and Methods:Thirty male Wistar rats, weighing 160-180 g, were divided into 6 groups of 5 rats each as follows; Group 1 received distilled water orally (0.2 ml a 100 g rats), daily, throughout the period of study. Group 2 received Cd alone (in the form of CdSO4) at 5 mg/kg/day via intraperitoneal route for 5 consecutive days. Group 3 were pre-treated with Cd as Group 2 and thereafter left untreated for a period of 4-week. After the oral lethal dose of PEVA was determined, Groups 4, 5, and 6 received graded doses of PEVA at 100, 200 and 400 mg/kg/day (0.2 ml per 100 g rats), respectively via oral route for 4 weeks after they were pre-treated with Cd as Group 2. Blood samples were collected for some plasma biochemical assays while urine samples were collected using metabolic cages.Results:PEVA administration significantly increased (P < 0.05) the body weight and feeding patterns that were significantly reduced (P < 0.05) by Cd toxicity. PEVA also significantly reinstated the plasma antioxidant status, as well as glucose and urine volume of the rats toward control values (P < 0.05).Conclusion:PEVA can be an herbal alternative in the treatment or management of subjects manifesting alterations in feeding pattern and urine volume that is Cd-induced.

Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats.

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.

The comparison of the effects of acute and repeated morphine administration on fast synaptic transmission in magnocellular neurons of supraoptic nucleus, plasma vasopressin levels, and urine volume of male rats.

The activity of the magnocellular neurons (MCNs) of supraoptic nucleus (SON) is regulated by a variety of excitatory and inhibitory inputs. Opioids are one of the important compounds that affect these inputs at SON synapses. In this study, whole-cell patch clamp recording of SON neurons was used to investigate the effect of acute and repeated morphine administration on spontaneous inhibitory and excitatory post synaptic currents (sIPSCs and sEPSCs) in MCNs. While acute bath application of morphine to brain slice of intact rat produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency, repeated in-vivo administration of morphine produced opposite effect. Moreover, repetitive i.c.v. administration of morphine for three consecutive days caused significant increase in urine volume, but had no significant alteration in water consumption compared to control group. The increase in urine volume was consistent with a significant decrease in plasma arginine vasopressin (AVP) levels after repetitive i.p. morphine administration. The results suggest that acute administration of morphine stimulates whereas repeated administration of morphine inhibits the MCNs. Morphine-induced MCN inhibition could result in diminished plasma AVP levels and eventually an increase in urine volume of rats.

Association between Melatonin Secretion and Nocturia in Elderly Individuals: a Cross-Sectional Study of the HEIJO-KYO Cohort

Nocturnal voids are regulated by circadian biological rhythms, including decreased urine production and increased bladder storage capacity at night. A previous experimental study suggested that exogenous melatonin decreases urine production and increases bladder capacity in rats. However, little is known about whether melatonin secretion, which is considerably lower than exogenous melatonin, is associated with nocturia in humans. We evaluated the association between melatonin secretion and nocturia. In this cross-sectional study we examined 861 community based elderly individuals with a mean age of 72.1 years. We measured nocturnal void frequency and overnight urinary 6-sulfatoxymelatonin excretion as an index of melatonin secretion. Nocturia was defined as 2 or more nocturnal voids. Univariate comparisons between the 261 and 600 study participants with and without nocturia, respectively, showed marginal to significant associations of nocturia with age, gender, body mass index, estimated glomerular filtration rate, calcium channel blockers, benign prostatic hyperplasia, total voided urine volume, urinary 6-sulfatoxymelatonin, duration in bed, day length, and daytime and nighttime physical activity. The multivariate logistic regression model adjusted for the former confounding factors revealed that higher urinary 6-sulfatoxymelatonin was significantly associated with a lower nocturia OR (adjusted OR 0.73, 95% CI 0.56-0.96, p=0.023). After adjustment for age, gender and duration in bed the mean volume of a single voided urine significantly increased with tertiles of increasing urinary 6-sulfatoxymelatonin (p for trend=0.022). Melatonin secretion is significantly and inversely associated with nocturia in a general elderly population.

Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume. Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration. Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed. Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Effect of triterpene saponins from roots of Ampelozizyphus amazonicus Ducke on diuresis in rats

Ethnopharmacological relevance Ampelozizyphus amazonicus Ducke is a plant used in Brazilian folk medicine to both prevent malaria and act as a depurative. Aim of the study We have investigated the effects of an ethanol crude extract of roots of Ampelozizyphus amazonicus (CE AaD), a chemically characterized saponin mixture (SAP AaD), as well as a saponin-free fraction (SAP AaD-free) obtained from CE AaD on diuresis in rats. Materials and methods Wistar rats under ad libitum water conditions or water deprivation for 12 h prior to the start of the experiment were volume-expanded with 0.9% NaCl (4% body weight, by gavage) containing either CE AaD, SAP AaD, or SAP AaD-free at the doses indicated in the text. Rats were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). Results CE AaD increased urine volume in rats under conditions of both free access to water and under water deprivation. In the latter condition, CE AaD (150 mg/kg) increased the urine volume from zero to 0.9 ± 0.1 ml/120 min, n = 6). Similarly, the SAP AaD-free (50–200 mg/kg) mixture also increased the urine volume. In contrast, SAP AaD (12.5–1000 mg/kg) produced a significant reduction ( p < 0.01) in diuresis under conditions of both water deprivation and with free access to water prior to the start of the experiment. Conclusion Our data indicate that CE AaD contains compounds that cause both diuresis and antidiuresis and that the antidiuretic effect is due mainly to the presence of saponins.

Centrally and Peripherally Administered Ghrelin Potently Inhibits Water Intake in Rats

Ghrelin is known as a potent orexigenic hormone through its action on the brain. In this study, we examined the effects of intracerebroventricular (icv) and iv injection of ghrelin on water intake, food intake, and urine volume in rats deprived of water for 24 h. Water intake that occurred after water deprivation was significantly inhibited by icv injection of ghrelin (0.1, 1, and 10 nmol/rat) in a dose-related manner, although food intake was stimulated by the hormone. The antidipsogenic effect was as potent as the orexigenic effect. Similarly, water intake was inhibited, whereas food intake was stimulated dose dependently after iv injection of ghrelin (0.1, 1, and 10 nmol/kg). The inhibition of drinking was comparable with, or even more potent than, atrial natriuretic peptide (ANP), an established antidipsogenic hormone, when administered icv, although the antidipsogenic effect lasted longer. ANP had no effect on food intake. Urine volume decreased dose relatedly after icv injection of ghrelin but not by ANP. Intravenous injection of ghrelin had no effect on urine volume. Because drinking usually occurs with feeding, food was withdrawn to remove the prandial drinking. Then the antidipsogenic effect of ghrelin became more potent than that of ANP and continued longer than when food was available. Expression of Fos was increased in the area postrema and the nucleus of the tractus solitarius by using immunohistochemistry after icv and iv injection of ghrelin. The present study convincingly showed that ghrelin is a potent antidisogenic peptide in rats.

高齢者夜間頻尿における脳性ナトリウム利尿ペプチド (BNP) と相対的夜間多尿の関連

In addition to overactive bladder (OAB) and sleep disorders (disturbance of additional sleep induction), nocturnal polyuria has been reported as an etiology of nocturia in elderly people. To investigate the influence of heart function on nocturnal polyuria in elderly people, we examined the association with nocturnal polyuria using brain natoriuretic peptide (BNP), which are useful for evaluating the prognosis of heart failure. The patients were 128 patients (92 males, 36 females) who were treated for nocturia in Kohsei general hospital and other relative hospital between October 2002 and September 2005. We measured BNP levels at physical examination. Simultaneously, the patients were instructed to write a frequency volume chart (FVC) for 4 days. 24-hour urine volume, Daytime urine volume, nocturnal (sleep) urine volume, nocturnal polyuria index (NPi) were calculated from FVC. The association was examined. However, alphal-blockers or anticholinergic agents that had been prescribed to treat urination disorders were continuously administered. Overall, the mean BNP level was high, 46.3+/-39.6 pg/ml. The mean 24-hour urine volume was 1,555+/- 458 ml. The mean daytime urine volume was 935+/-322 ml. The mean nocturnal urine volume was 624+/-251 ml. The mean nocturnal urine volume rate was high, 40.1 - 10.5%. However, there was a close association between BNP and the 24-hour urine volume (p = 0.0215), the daytime urine volume (p = 0.0004), the NPi (p = 0.0003). The daytime urine volume decreased with the BNP level. The NPi increased with the BNP level. Patients were divided into 2 groups, a group with a BNP level less than 50 pg/ml and a group with a BNP level of 50 pg/ml or more. In the group with a BNP level less than 50 pg/ml, the nocturnal urine volume rate was 38.14+/-10.07%. In the group with a BNP level of 50 pg/ml or more, the rate was significantly higher (43.97+/-10.48%, p<0.0029). These results suggest that many elderly patients latently have mild heart failure, and that relative nocturnal polyuria reduces cardiac load. Therefore, in patients with a high BNP level, administration of antidiuretic hormone to decrease nocturnal urine volume is risky. Administration of diuretics during the afternoon or evening may be safer.

EFFECTS OF THE SELECTIVE ACETYLCHOLINESTERASE INHIBITOR TAK-802 ON THE VOIDING BEHAVIOR AND BLADDER MASS INCREASE IN RATS WITH PARTIAL BLADDER OUTLET OBSTRUCTION

We examined the effects of the selective acetylcholinesterase (AChE) inhibitor TAK-802 on voiding behavior and residual urine volume in rats with partial bladder outlet obstruction (BOO) vs rats treated with the nonselective AChE inhibitor distigmine and the muscarinic agonist bethanechol. In addition, the effect of repeat doses of TAK-802 on the bladder mass increase associated with BOO was also examined. Male rats with BOO were used. Six to 8 days after obstruction voiding behavior was observed in a metabolic cage. The animals were then treated orally with 1 drug, and voiding frequency and urine volume at each void were measured for 3 hours. Subsequently the volume of urine retained in the bladder (residual urine) was measured. In another experiment bladder weight in rats with BOO was measured after early repeat doses of TAK-802. BOO increased voiding frequency and decreased average voided volume. TAK-802 and distigmine increased average voided volume, while not causing any change in voiding frequency. On the other hand, bethanechol increased voiding frequency without affecting average voided volume. While all 3 drugs significantly decreased residual urine volume, TAK-802 was most efficacious. In addition, bladder weight in the control BOO group was greater (approximately 2.2-fold) than that in the sham operated group and early repeat administration of TAK-802 prevented the bladder mass increase. AChE inhibitors decreased residual urine volume by restoring voiding function in rats with BOO, although only the effect of TAK-802 was dose dependent. Bethanechol also decreased residual urine volume in a dose dependent manner but by increasing voiding frequency. The prevention of a bladder mass increase by TAK-802 treatment may be attributable to its effect on restoring voiding.

Evidence for central venous pressure resetting during initial exposure to microgravity.

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.

Antiurolithiatic Activity of 7-Hydroxy-2′,4′,5′- Trimethoxyisoflavone and 7-Hydroxy-4′ -Methoxyisoflavone from Eysenhardtia polystachya

ABSTRACT The antilithiatic and diuretic activity of 7-hydroxy-2′,4′,5′-trimethoxyisoflavone and 7-hydroxy-4′-methoxyisoflavone, isolated in aqueous extracts of the heartwood of Eysenhardtia polystachya, was tested in rats by observing calculus formation (experimentally induced by implantation of a zinc disc in the urinary bladder) and urine production. A significant decrease in urinary stone size was observed in animals treated with the compounds as compared with animals in control groups. The compounds also increased 24 h urine volume in rats as compared with the control animals not receiving the test compounds.