Urinary Excretion Of Na Research Articles

Rh versus pH: the role of Rhesus glycoproteins in renal ammonia excretion during metabolic acidosis in a freshwater teleost fish.

Increased renal ammonia excretion in response to metabolic acidosis is thought to be a conserved response in vertebrates. We tested the hypothesis that Rhesus (Rh) glycoproteins in the kidney of the freshwater common carp, Cyprinus carpio, play a crucial role in regulating renal ammonia excretion during chronic metabolic acidosis. Exposure to water pH 4.0 (72 h) resulted in a classic metabolic acidosis with reduced plasma arterial pH and [HCO3(-)], no change in PCO2 and large changes in renal function. Urine [NH4(+)] as well as [titratable acidity-HCO3(-)] rose significantly over the acid exposure, but the profound reduction (fivefold) in urine flow rates eliminated the expected elevations in renal ammonia excretion. Low urine flow rates may be a primary strategy to conserve ions, as urinary excretion rates of Na(+), Cl(-) and Ca(2+) were significantly lower during the acid exposure relative to the control period. Interestingly, renal Rhcg1 mRNA and protein levels were elevated in acid-exposed relative to control groups, along with mRNA levels of several ion transporters, including the Na(+)/H(+) exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. Immunofluorescence microscopy showed a strong apical Rhcg1 signal in distal tubules. Taken together, these data show that renal Rh glycoproteins and associated ion transporters are responsive to metabolic acidosis, but conservation of ions through reduced urine flow rates takes primacy over renal acid-base regulation in the freshwater C. carpio. We propose that an 'acid/base-ion balance' compromise explains the variable renal responses to metabolic acidosis in freshwater teleosts.

Nephroprotective, Diuretic and Antioxidant Effects of Some Medicinal Herbs in Gentamicin-Nephrotoxic Rats

Aim: To investigate the nephroprotective, diuretic and antioxidant effects of extracts of Petroselinum sativum, Eruca sativa and Curcuma longa herbs in gentamicin (GM)-nephrotoxic rats. Material and Methods: Forty two adult male Sprague Dawley rats were randomly distributed into six equal groups. Group 1 was given sterile saline solution by intraperitoneal (i.p.) injection (negative control). Group 2 (nephrotoxic) was injected with GM (80 mg/kg, i.p.) for 8 days during the last week of the experiment. Groups 3, 4, 5 and 6 were orally pretreated with herbs extracts, alone and in combination, for 6 weeks along with GM during the last week. Blood and urine samples were collected for biochemical analyses. Kidney specimens were taken for estimating oxidant/antioxidant parameters and for histopathology. Results: GM induced nephrotoxicity characterized by biochemical and histopathological alterations, increased lipid peroxidation and reduced activity of antioxidant enzymes in kidney tissues. Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa herbs caused nephroprotective effect as it decreased in the elevated serum urea, creatinine and alkaline phosphatase (ALP) activity and normalized serum levels of Na+ and K+ electrolytes in GM-intoxicated rats. These extracts also increased the urine volume and urinary excretion of Na+ and K+, ameliorated renal tubular necrosis and increased activities of renal antioxidant enzymes in GM-intoxicated rats. Conclusion: Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa produce nephroprotective, diuretic and antioxidant effects in GM - nephrotoxic rats. These herbs may be beneficial for patients who suffer from kidney diseases and those on GM therapy.

Yeast exposure in the preparation of steamed rehmannia root improving its effects on alloxan-induced diabetic rats

Ethnopharmacological relevanceThe root of Rehmannia glutinosa (Gaertn.) DC. has been used in China for more than 2000 years to treat various diseases including diabetes mellitus (DM) and its complications. Steamed rehmannia root (SRR) is one of the mainly used forms. During its preparation, the material has the chance to be exposed to microorganisms, particularly yeast. The aim of this study is to verify the effect of SRR on diabetes complications and the necessity of yeast exposure. Materials and methodsWater extract of SRR was incubated with alcohol yeast to obtain fermented SRR (FSRR). Alloxan-induced diabetic rats were administrated with medicated animal chows for 8 weeks. Urine volume, fasted blood glucose and food intake were monitored, and open field test and tail immersion test were conducted in the last week, plasma and urine samples were subjected to biochemical examinations. ResultsIn DM rats, defecation in open field test was found reduced, and tail flick latency in tail immersion test increased. In the meantime, urinary excretions of Na+, K+, aldosterone, albumin and creatinine increased, and plasma concentrations of Na+, K+ and creatinine reduced and those of aldosterone, TXB2/6-Keto-PGF1α and urea nitrogen elevated. Most of these indicators were significantly improved by FSRR administration, but the effects of SRR were relatively inferior in several aspects. However, SRR and FSRR could not improve the typical symptoms of DM. ConclusionsOur data demonstrated that both SRR and FSRR have no obvious hypoglycemic effect, but have the potential to prevent the onset and development of diabetes complications, and this function can be improved by yeast exposure.

Abstract 558: Role of Angiotensin Converting Enzyme 2/angiotensin (1-7)/mas Axis in the Hypotensive Effect of Azilsartan

Objective: The possible counteracting effect of angiotensin (Ang)-converting enzyme (ACE)2/Ang (1-7)/Mas axis against the ACE/Ang II/ Ang II type 1 (AT 1 ) receptor axis in blood pressure control has been highlighted. We examined the possibility that this axis might be involved in the anti-hypertensive effect of newly developed Ang II type 1 (AT 1 ) receptor blocker (ARB), azilsartan, in comparison with olmesartan. Methods: Human renin (hRN) and human angiotensinogen (hANG) double transgenic mice (hRN/hANG-Tg) were used. Ten-week-old male hRN/hANG-Tg mice were administrated control chow or three different doses (1, 5 and 10mg/kg/day) of ARBs, azilsartan or olmesartan in chow for 4 weeks. Blood pressure was analyzed by radio telemetry method before drug administration and every two weeks after medication. Four weeks after drug administration, expression of ACE2 mRNA level was assessed by real time RT-PCR method. Results: Blood pressure was significantly higher in hRN/hANG-Tg mice compared with that in wild type (WT) mice. Treatment with all doses of azilsartan decreased blood pressure to the level of WT mice. Treatment with olmesartan (1 mg/kg/day) decreased blood pressure; however, this decrease was weaker than that with azilsartan at the same dose. Olmesartan (5 and 10 mg/kg/day) decreased blood pressure to the WT mice level; however, the reduction of blood pressure in the night-time was stronger in azilsartan group. Expression of ACE2 mRNA was decreased in heart and kidney of hRN/hANG-Tg mice compared with WT mice. This decrease in ACE2 mRNA expression was attenuated by administration of azilsartan, but not by olmesartan treatment. The ratio of heart to body weight ratio was decreased in all azilsartan-treated groups, but this decrease was observed only in 10 mg/kg/day of olmesartan-treated group. Treatment with azilsartan even at lower dose increased the urinary excretion of Na. Conclusion: These results suggested that hypotensive effect of azilsartan may involve the activation of ACE2/Ang(1-7)/Mas axis with AT 1 receptor blockade. Further investigation will reveal the pathophysiological role of ACE2/Ang(1-7)/Mas axis in blood ptessure control and contribute to discuss further the possible drug effect of ARBs beyond class effect.

Non-Natriuretic Doses of Furosemide: Potential Use for Decreasing the Workload of the Renal Outer Medulla with Minimal Magnesium Wasting in the Rat

Background/Aims: Since furosemide (FS) inhibits active Na⁺ reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O₂ supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg²⁺). Mg²⁺ is important because the ATP needed to perform work must have bound Mg²⁺ to it. Methods: Rats were injected intraperitoneally with a range of doses of FS. The measured outcomes were urine flow rate and parameters of functions of the mTAL (i.e. urine and renal papillary osmolality and urinary excretion of Na⁺, Cl^-, K⁺ and Mg²⁺, and concentrations of Mg²⁺ in serum). Results: The urine flow rate increased significantly starting at 2.4 mg FS/kg. The renal papillary osmolality decreased at ≥0.4 mg FS/kg, and the large detectable natriuresis started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg²⁺ rose significantly. Conclusion: In rats, the non-natriuretic dose of FS may reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL appears to be a decrease in urine osmolality rather than a rise in urine flow rate. Higher doses of FS should be avoided, as they induce high rates of Mg²⁺ excretion, which can deplete the body of this essential electrolyte.

Response of the Renal Inner Medulla to Hypoxia: Possible Defense Mechanisms

Background/Aims: Owing to the precarious blood supply to the renal medulla and the high metabolic requirement of the medullary thick ascending limb of Henle’s loop, this nephron segment should be especially vulnerable when its supply of O₂ declines. Methods: Rats were exposed to 8 or 21% O₂ at different time points up to 5 h, and samples were collected for urine flow rate, urine (U_osm) and renal papillary (RP_osm) osmolality, urinary excretion of Na⁺, Cl^–, K⁺ and Mg²⁺, blood gases, erythropoietin and vasopressinase activity in plasma. Other groups of rats were pretreated with desmopressin acetate (dDAVP) or underwent bilateral nephrectomy (BNX) 1 h prior to the exposure. Results: Hypoxic rats had water diuresis (WD) within 2.5 h, as evidenced by lower U_osm (333 ± 42 mosm/l) and RP_osm (869 ± 57 mosm/l), thus suggesting that hypoxia led to a failure to achieve osmotic equilibrium within the renal papilla. Circulating vasopressinase activity increased, which was partially renal in origin because it was lower after BNX. The renal concentrating ability during hypoxia was maintained with dDAVP pretreatment, suggesting that dDAVP may have improved O₂ delivery and the active reabsorption of Na⁺ in the renal medullary region. Conclusions: WD or high vasopressinase activity may be valuable diagnostic tools to assess renal medullary hypoxia. Pretreatment with dDAVP may prevent these changes during hypoxia.

Increased expression of renal TRPM6 compensates for Mg(2+) wasting during furosemide treatment.

BackgroundFurosemide is a loop diuretic, which blocks the Na+, K+, 2Cl− cotransporter (NKCC2) in the thick ascending limb of Henle (TAL). By diminishing sodium (Na+) reabsorption, loop diuretics reduce the lumen-positive transepithelial voltage and consequently diminish paracellular transport of magnesium (Mg2+) and calcium (Ca2+) in TAL. Indeed, furosemide promotes urinary Mg2+ excretion; however, it is unclear whether this leads, especially during prolonged treatment, to hypomagnesaemia. The aim of the present study was, therefore, to determine the effect of chronic furosemide application on renal Mg2+ handling in mice.MethodsTwo groups of 10 mice received an osmotic minipump subcutaneously for 7 days with vehicle or 30 mg/kg/day furosemide. Serum and urine electrolyte concentrations were determined. Next, renal mRNA levels of the epithelial Mg2+ channel (TRPM6), the Na+, Cl− cotransporter (NCC), the epithelial Ca2+ channel (TRPV5), the cytosolic Ca2+-binding protein calbindin-D28K, as well parvalbumin (PV), claudin-7 (CLDN7) and claudin-8 (CLDN8), the epithelial Na+ channel (ENaC) and the Na+–H+ exchanger 3 (NHE3) were determined by real-time quantitative polymerase chain reaction. Renal protein levels of NCC, TRPV5, calbindin-D28K and ENaC were also measured using semi-quantitative immunohistochemistry and immunoblotting.ResultsThe mice chronically treated with 30 mg/kg/day furosemide displayed a significant polyuria (2.1 ± 0.3 and 1.3 ± 0.2 mL/24 h, furosemide versus control respectively, P < 0.05). Furosemide treatment resulted in increased serum concentrations of Na+ [158 ± 3 (treated) and 147 ± 1 mmol/L (control), P < 0.01], whereas serum K+, Ca2+ and Mg2+ values were not significantly altered in mice treated with furosemide. Urinary excretion of Na+, K+, Ca2+ and Mg2+ was not affected by chronic furosemide treatment. The present study shows specific renal upregulation of TRPM6, NCC, TRPV5 and calbindin-D28K.ConclusionsDuring chronic furosemide treatment, enhanced active reabsorption of Mg2+ via the epithelial channel TRPM6 in DCT compensates for the reduced reabsorption of Mg2+ in TAL.

Mice with targeted disruption of the acyl-CoA binding protein display attenuated urine concentrating ability and diminished renal aquaporin-3 abundance

The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long-chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium, with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Interestingly, however, water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared with that of (+/+) mice. Subsequent to 20-h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit, and higher relative weight loss compared with (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone, and aldosterone between mice of the two genotypes. After water deprivation, renal medullary interstitial fluid osmolality and concentrations of Na(+), K(+), and urea did not differ between genotypes and cAMP excretion was similar. Renal aquaporin-1 (AQP1), -2, and -4 protein abundances did not differ between water-deprived (+/+) and ACBP(-/-) mice; however, ACBP(-/-) mice displayed increased apical targeting of pS256-AQP2. AQP3 abundance was lower in ACBP(-/-) mice than in (+/+) control animals. Thus we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3, leading to impaired efflux over the basolateral membrane of the collecting duct.

Effects of BMI on Blood Pressure and Urinary Excretion of Sodium, Chloride and Potassium in Young Paraguayans

Background: Obesity has been associated with an increased risk for coronary disease, type 2 diabetes, hyperlipidemia and mortality. The demographics of Paraguay show that most of the population is of mixed European and Amerindian descent. Most of the studies performed in Hispanics, particularly in the United States fail to identify their country of origin. There is a paucity of data in Paraguay about the relationship between BMI and BP in young adults. Furthermore, there is an increased prevalence of overweight, obesity and hypertension in the country. In this study, we hypothesized that even early increments of BMI are associated with increased blood pressure (BP) readings in young adults in Paraguay. Methods: Cross-sectional study, performed in 72 adult participants, from Asuncion Paraguay. There is no similar study published in this country. BMI, BP readings and urinary excretion of Na, K and Cl were studied. Results: Mean age 25. 2 ± 1.52 years. Mean BMI 24.1 ± 3.66. There was a linear relationship between BMI and SBP, DBP, MAP and urine Na, K and Cl across all levels. A multivariate analysis, adjusting for gender, showed that increased BMI is associated with increased BP readings. A BMI of 23.4 was the best cut-off for a BP equal or higher than 135/85 mmHg (pre- hypertension), (AUC = 0.80). A BMI of 24.2 was the best cut off for a BP equal or higher than 140/90 (AUC = 0.80). After excluding participants with SBP equal or higher than 140 mmHg and DBP equal or higher than 90 mmHg, BMI was still associated with increased SBP and DBP even in normotensive individuals. After excluding obese and overweight patients, we found that even a small increase of BMI was associated with an increase in blood pressure. Conclusions : BMI values of 24.2 and 23.4 were associated with BP of 140/90 and 135/85 respectively. Since the BMI cut-off for obesity was established in different cohorts, we might need to create a more specific set of values for the Paraguayan population, as the values proposed by the American Heart Association are probably rather high for this population. doi:10.4021/wjnu8e

The antihypertensive effect of ethyl acetate extract of radish leaves in spontaneously hypertensive rats.

Radish (Raphanus sativus L.) is a cruciferous vegetable, and its leaves have antioxidant and anticancer properties. This study was conducted to evaluate the effects of ethyl acetate extracts from radish leaves on hypertension in 11-week-old spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into 3 groups of 6 rats each on the basis of initial systolic blood pressure (SBP) and were treated with oral administration of radish leaf extract (0, 30, or 90 mg/kg body weight [bw], respectively) for 5 weeks. Six Wistar rats were used as normotensive controls. The amount of the radish leaf extract had no effect on body weight. The SBP of the SHRs showed a decreasing trend with the consumption of the radish leaf extract. In the third week, the SBP of the group fed 90 mg extract/kg bw reduced from 214 mmHg to 166 mmHg and was significantly lower than that of the normotensive and hypertensive controls. The extract did not show a significant effect on the angiotensin-converting enzyme (ACE) activity in the serum, kidney, and lung. The extract increased the concentration of NO in serum and the activities of antioxidant enzymes such as glutathione peroxidase and catalase in red blood cells (RBCs). The serum concentrations of Na+ and K+ were not significantly different between all groups. However, the fecal concentrations of Na+ and K+ increased; the fecal concentrations of Na+ and K+ for the normotensive and hypertensive controls were not different. Urinary excretion of Na+ was higher in the normotensive Wistar rats than in the SHRs, while that of K+ was not significantly different. These findings indicate that consumption of radish leaves might have had antihypertensive effects in SHRs by increasing the serum concentration of NO and fecal concentration of Na+ and enhancing antioxidant activities.

EMD638683, a Novel SGK Inhibitor with Antihypertensive Potency

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is transcriptionally upregulated by mineralocorticoids and activated by insulin. The kinase enhances renal tubular Na+-reabsorption and accounts for blood pressure increase following high salt diet in mice made hyperinsulinemic by dietary fructose or fat. The present study describes the in vitro and in vivo efficacy of a novel SGK1 inhibitor (EMD638683). EMD638683 was tested in vitro by determination of SGK1-dependent phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1) in human cervical carcinoma HeLa-cells. In vivo EMD638683 (4460 ppm in chow, i.e. approx. 600 mg/kg/day) was administered to mice drinking tap water or isotonic saline containing 10% fructose. Blood pressure was determined by the tail cuff method, and urinary electrolyte (flame photometry) concentrations determined in metabolic cages. In vitro testing disclosed EMD638683 as a SGK1 inhibitor with an IC50 of 3 µM. Within 24 hours in vivo EMD638683 treatment significantly decreased blood pressure in fructose/saline-treated mice but not in control animals or in SGK1 knockout mice. EMD638683 failed to alter the blood pressure in SGK1 knockout mice. Following chronic (4 weeks) fructose/high salt treatment, additional EMD638683 treatment again decreased blood pressure. EMD638683 thus abrogates the salt sensitivity of blood pressure in hyperinsulinism without appreciably affecting blood pressure in the absence of hyperinsulinism. EMD638683 tended to increase fluid intake and urinary excretion of Na⁺, significantly increased urinary flow rate and significantly decreased body weight. Conclusion: EMD638683 could serve as a template for drugs counteracting hypertension in individuals with type II diabetes and metabolic syndrome.

Antihypertensive effects of the methylene chloride leaf extract of &lt;i&gt;Celtis durandii&lt;/i&gt; Engler (Ulmaceae) on rats

Celtis durandii (Ulmaceae), one of the plants used in traditional medicine to cure migraine, epilepsy,and high blood pressure, was administrated as antihypertensive in normotensive rats (NTR) and hypertensive saline rats (HSR). The antihypertensive effects of the methylene chloride extract of the plant were evaluated in NTR and HSR by the invasive method. Results indicated that C. durandii induce a decreased blood pressure after administration of the extract. This sudden decrease was followed by a slight increase, and then by an antihypertensive late activity of the extract that lasted for one hour. At a dose of 20 mg/kg, the antihypertensive late activity of C. durandii extract was 42% in NTR and 65.21% in HSR. The urinary excretion of Na+ increased by 260% and 475% respectively in NTR and HSR at the dose of 300 mg/kg while that of K+ increased by 260% and 123% in the same animals at the same dose. The results suggest that C durandii possesses an antihypertensive activity that could result from its diuretic effects. This activity could be explained by decrease of surrounding resistances.Keywords : Celtis durandii, Blood pressure, Hypotension, Diuretic, Rat .

Renal aging in WKY rats: Changes in Na +,K +-ATPase function and oxidative stress

It has been suggested that alterations in Na +,K +-ATPase mediate the development of several aging-related pathologies, such as hypertension and diabetes. Thus, we evaluated Na +,K +-ATPase function and H 2O 2 production in the renal cortex and medulla of Wistar Kyoto (WKY) rats at 13, 52 and 91 weeks of age. Creatinine clearance, proteinuria, urinary excretion of Na + and K + and fractional excretion of Na + were also determined. The results show that at 91 weeks old WKY rats had increased creatinine clearance and did not have proteinuria. Despite aging having had no effect on urinary Na + excretion, urinary K + excretion was increased and fractional Na + excretion was decreased with age. In renal proximal tubules and isolated renal cortical cells, 91 week old rats had decreased Na +,K +-ATPase activity when compared to 13 and 52 week old rats. In renal medulla, 91 week old rats had increased Na +,K +-ATPase activity, paralleled by an increase in protein expression of α 1-subunit of Na +,K +-ATPase. In addition, renal H 2O 2 production increased with age and at 91 weeks of age renal medulla H 2O 2 production was significantly higher than renal cortex production. The present work demonstrates that although at 91 weeks of age WKY rats were able to maintain Na + homeostasis, aging was accompanied by alterations in renal Na +,K +-ATPase function. The observed increase in oxidative stress may account, in part, for the observed changes. Possibly, altered Na +,K +-ATPase renal function may precede the development of age-related pathologies and loss of renal function.

Antihypertensive effects of the aqueous extract leaves of celtis durandii engler (ulmaceae) on rat

Celtis durandii (Ulmaceae), one of the plants used in traditional medicine to cure migraine, epilepsy, and high blood pressure was evaluated for antihypertensive activity in normotensive rats (NTR) and hypertensive saline rats (HSR), by the invasive method. Results indicated that C. durandii induce a decreased blood pressure after administration of the extract. This sudden decrease is followed by a slight increase, and then by an antihypertensive late activity of the extract that lasts for one hour. At a dose of 35 mg /kg, the antihypertensive late activity of C. durandii extract was 40% in NTR and 36% in HSR. The urinary excretion of Na+ increased by 513 % and 913%, respectively, in NTR and HSR at dose of 300 mg/kg while that of K+ increased by 82 % and 212% in the same animals at same dose. The results suggest that C durandii possesses an antihypertensive activity that could result from its diuretic effects. This activity could be explained by decrease of surrounding resistances.Key words: Celtis durandii, blood pressure, diuretic, rat.

Effects of Bungarus candidus (Malayan krait) venom on general circulation and renal hemodynamics in experimental animals

Abstract Background: Many studies have reported the occurrence of lethal acute renal failure after snakebites. Bungarus candidus (Malayan krait) is a medically important venomous snake distributed widely throughout Southeast Asia. The best known features of systemic envenoming by B. candidus are neurotoxic. Objective: Obtain more information on effects of B. candidus venom on changes in systemic and renal hemodynamics in experimental animals. Methods: Twelve adult male New Zealand white rabbits were used to study the effect of B. candidus venom on general circulation and renal hemodynamics. An anesthetized animal was intravenously injected with B. candidus venom at a dosage of 50μg/kg bodyweight. All changes of parameters were observed after initial post venom injection and recorded at 30 min intervals until 150 minutes after envenomation. Results: After envenomation, cardiovascular responses showed a marked decrease in mean arterial pressure within two minutes, afterwards gradually returning closely to baseline values. There were stepwise decreases in heart rate and cardiac output, while total peripheral resistance was slightly increased. The renal hemodynamics significantly decreased by glomerular filtration rate, effective renal plasma flow and effective renal blood flow, while the filtration fraction significantly increased. Envenomed animals showed a reduction in renal fraction, while renal vascular resistance stepwise increased. The plasma potassium level tended to increase. Animals showed stepwise decreases in urinary excretion of Na+, K+ and Cl-. A marked decrease in plasma calcium level was apparent at 120 minutes, while plasma creatine phosphokinase and lactate dehydrogenase levels increased at 30-120 minutes. Conclusion: A significant drop in blood pressure was attributed to a sustained fall in cardiac output, which would be associated with a reduction in heart rate. Sustained hypotension would contribute to reduction of renal blood flow, which results in decreased GFR.

Altered renal proximal tubular endocytosis and histology in mice lacking myosin‐VI

Myosin VI (Myo6) is an actin-based molecular motor involved in clathrin-mediated endocytosis that is highly expressed in the renal proximal tubule brush border. We investigated the renal physiological consequences of loss of Myo6 function by performing renal clearance and physiological measurements on Myo6 functional null Snell's waltzer (sv/sv) and control heterozygous (+/sv) mice. Sv/sv mice showed reduced body weight and elevated blood pressure compared with controls; no differences were observed for glomerular flow rate, urine volume, blood acid-base parameters, and plasma concentrations and urinary excretions of Na(+) and K(+). To assess the integrity of endocytosis-mediated protein absorption by the kidney, urinary albumin excretion was measured, and the proximal tubular uptake of intravenously injected endocytic marker horseradish peroxidase (HRP) was examined. Albumin excretion was increased nearly 4-fold in sv/sv mice relative to controls. Conversely, HRP uptake was reduced and delayed in proximal tubule cells of the sv/sv kidney observed by electron microscopy at 5 and 30 min after injection. Consistent with impaired endocytosis, we also observed defects indicating alterations along the endocytic pathway in sv/sv proximal tubule cells: (1) decreased membrane association of the clathrin adaptor subunit, adaptin beta, and Disabled-2 (Dab2) after sedimentation of renal homogenates and (2) reduced apical vacuole number. In addition, proximal tubular dilation and fibrosis, likely secondary effects of the loss of Myo6, were observed in sv/sv kidneys. These results indicate that Myo6 plays a key role in endocytosis-mediated protein absorption in the mouse kidney proximal tubule.

Salt intake in young Swedish men

To measure dietary salt intake in a Swedish population. A cross-sectional study with measured 24 h urinary excretion of Na and K. Completeness of urine collection was assessed using p-aminobenzoic acid. The subjects were interviewed on their habitual food intake. Sahlgrenska University Hospital, Gothenburg, Sweden. Eighty-six young men (age 18-20 years), randomly selected from the population of Gothenburg. Seven men were excluded due to incomplete urine collection. The mean excretion of Na and K over 24 h was 198 and 84 mmol, respectively (corresponding to 11.5 g NaCl and 3.3 g K). The mean 24 h excretion in the highest quartile of Na excretion was 297 mmol Na and 105 mmol K, and in the lowest quartile, 100 mmol Na and 68 mmol K. The mean Na:K ratio was 2.3, and respectively 3.2 and 1.8 in the highest and lowest Na excretion quartiles. Calculated energy intake did not differ between the highest and lowest quartiles of Na excretion, but body weight, BMI and the intake of certain foods known to be Na-rich did. Salt intake in young men was alarming high and even subjects in the lowest quartile of Na excretion did not meet present recommendations to limit salt intake to 5-6 g/d. At this point we can only speculate what the consequences of the high salt intake may be for CVD and stroke later in life. Regulation of the salt content in processed and fast food and in snacks is advocated, to curtail the salt burden on society imposed by the food industry.

Chronic undernutrition alters renal active Na+ transport in young rats: potential hidden basis for pathophysiological alterations in adulthood?

Epidemiological studies in the northeastern region of Brazil show an association between hypertension and malnutrition, especially in areas where protein-deficient diets are combined with high salt intake. We studied the consequences of a widely consumed deficient diet (basic regional diet, BRD), combined with high NaCl, on growth, renal Na+ and water handling and activities of ATP-dependent Na+ transporters in kidney proximal tubules. Young rats were fed after weaning with a low-protein and high-salt diet, which mimics that used in a vast region of Brazil. Body mass was evaluated from weaning up to the 19th week of age. Glomerular filtration rate, proximal Na+ reabsorption, distal Na+ delivery, urinary excretion of Na+ and water, and urine concentration capacity were evaluated from serum and urine concentrations of creatinine, Na+ and Li+, and by measurement of urinary volume and density. The (Na+ + K+)ATPase and the ouabain-insensitive Na+-ATPase were studied in vitro by measuring ATP hydrolysis. Expression of (Na+ + K+)ATPase was evaluated by immunodetection with the use of a specific antibody anti alpha1-catalytic subunit isoform. Undernourished rats reached early adulthood (14 weeks) with body and renal masses that were 2.3 times lower than controls. These rats became hypertensive (mean arterial pressure 18.7 +/- 0.6 kPa vs 15.5 +/- 0.9 kPa in control group) and showed augmented fractional proximal Na+ reabsorption (61.0 +/- 0.3% vs 81.8 +/- 2.2%) with a concomitant decrease in distal Na+ delivery (9.5 +/- 0.5 micromol/min vs 14.0 +/- 0.2 micromol/min per 100 g body weight). Urinary Na+ excretion was higher in BRD rats, (juvenile and adult) being however twice the increase in Na+ intake. The ATP-dependent Na+ transporters were affected in opposite ways. The (Na+ + K+)ATPase activity from undernourished rats fell by 30%, in parallel with a 20% decrease in its immunodetection, whereas the ouabain-insensitive Na+-ATPase, which is responsible for the fine-tune control of Na+ reabsorption, increased threefold. We conclude that early alterations in proximal tubule Na+ pumps, together with an abnormally augmented urinary Na+ excretion, might be the link between undernutrition and late renal dysfunction.

Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats

Tropaeolum majus L. (Tropaeolaceae), popularly known as “chaguinha”, is well recognized in Brazilian traditional medicine as diuretic agent, although no scientific data have been published to support this effect. Aim of the study To evaluate the diuretic activity of the infusion and the hydroethanolic extract (HETM) of Tropaeolum majus, and possible mechanism of action. Material and methods The infusions (2,5 – 10%) and the HETM doses (150, 300 mg/kg) were orally administered to rats. Urinary excretion, the electrolytes levels, and urea and creatinine were measured in of saline-loaded rats. Results The oral administration of 10% (corresponding to 500 mg/kg) of the infusion increased significantly the urinary Na + excretion. Only the oral administration of 300 mg/kg of HETM increased significantly the urinary and Na + excretion. Prolonged administration of the HETM (300 mg/kg) significantly increased diuresis and the urinary excretion of Na +, but others parameters were unaffected. To gain some evidence in possible involvement of prostaglandins system in diuretic action, the oral administration of HETM (300 mg/kg) in association indomethacin (5 mg/kg) reduced the urinary and sodium excretion when compared only HETM group. Conclusion The results suggest that HETM could present compound(s) responsible for diuretic activities with no signs of toxicity, and the mechanism could involve prostaglandin system.

Role of maternal glucocorticoid inducible kinase SGK1 in fetal programming of blood pressure in response to prenatal diet

Maternal stress and malnutrition modify intrauterine fetal development with impact on postnatal blood pressure, nutrient, water, and electrolyte metabolism. The present study explored the possible involvement of maternal serum- and glucocorticoid-inducible kinase (SGK)-1 in fetal programming of blood pressure. To this end, wild-type (sgk1(+/+)) male mice were mated with SGK1 knockout (sgk1(-/-)) female mice, and sgk1(-/-) males with sgk1(+/+) females, resulting in both cases in heterozygotic (sgk1(-/+)) offspring. Following prenatal protein restriction, the offspring of sgk1(+/+) mothers gained weight significantly slower and had significantly higher blood pressure after birth. Moreover, a sexual dimorphism was apparent in fasting blood glucose and plasma corticosterone concentrations, with higher levels in female offspring. In contrast, prenatal protein restriction of sgk1(-/-) mothers had no significant effect on postnatal weight gain, blood pressure, plasma glucose concentration, or corticosterone levels, irrespective of offspring sex. Plasma aldosterone concentration, urinary flow rates, and urinary excretions of Na(+) and K(+) were not significantly modified by either maternal genotype or nutritional manipulation. In conclusion, maternal signals mediated by SGK1 may play a decisive role in fetal programming of hypertension induced by prenatal protein restriction.