Search

Background: Artocarpus altilis, A. Champeden, and Artocarpus heterophylus are popular species in Indonesia, and are commonly used as traditional medicine. Objective: This study aims to evaluate the diuretic effects of the ethyl acetate fraction of these three species on normotensive Wistar rats. Methods: The ethyl acetate fraction was prepared by a liquid–liquid extraction method. To evaluate diuretic effects, the sixty rats were divided into normal (distilled water), negative (4.5% NaCl), positive control (furosemide 5 mg/kg), and the testing groups. The testing groups were orally given the ethyl acetate fraction of A. altilis, Artocarpus champeden, and A. heterophylus at three dose levels of 25, 50, and 100 mg/kg. All animals were orally given 4.5% NaCl at a dose of 2 mL/200 g except the normal group; then the animals were given drugs according to group doses. Urine volume and electrolyte levels produced by the testing groups were compared to those of the control group. The concentration and ratio of ions were calculated to determine the natriuretic and carbonic anhydrase activities. Results: The ethyl acetate fractions of the three Artocarpus species at 100 mg/kg dose were more active than the standard furosemide (p

Baccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. Investigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. Cladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. From LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. This study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed. [Display omitted] • Baccharis milleflora is a plant native to Brazil commonly used as a diuretic and antihypertensive. • We investigated the cardiorenal properties of the purified aqueous extract of B. milleflora (ESBM). • We identified 33 compounds in ESBM, including chlorogenic acid, glycosylated phenolic derivatives, flavones, and flavonols. • ESBM showed a significant diuretic and natriuretic effect without affecting renal potassium elimination. • These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. [ABSTRACT FROM AUTHOR]

We have previously demonstrated significant in vitro natriuretic effects of anandamide (AEA) nanoformulation in polymeric nanoparticles, whose size prevents their accumulation in organs, such as the kidneys. Therefore, it is of particular interest to design and test nanostructures that can pharmacologically accumulate in these organs. In this regard, we prepared and characterized polymeric nanomicelles (~14 and 40 nm). Likewise, their biodistribution was determined. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), n = 3 per group, were divided into five treatment conditions: control, sham, free AEA freshly dispersed in aqueous solution or 24 h after its dispersion, and AEA encapsulated in nanomicelles. The kidneys were the main site of accumulation of the nanoformulation after 24 h. Freshly dispersed free AEA showed its classical triphasic response in SHR, which was absent from all other treatments. Nanoformulated AEA produced a sustained antihypertensive effect over 2 h, accompanied by a significant increase in fractional sodium excretion (FSE %). These effects were not observed in WKY, sham, or free AEA-treated rats after 24 h of its aqueous dispersion. Without precedent, we demonstrate in vivo natriuretic, diuretic, and hypotensive effects of AEA nanoformulation in polymeric nanomicelles, suggesting its possible use as a new antihypertensive agent with intravenous administration and passive renal accumulation. [ABSTRACT FROM AUTHOR]

Abstract Background The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom or mucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Results Transcriptomes were constructed for the following families and species: Colubridae - Helicops leopardinus, Heterodon nasicus, Rhabdophis subminiatus; Homalopsidae – Homalopsis buccata; Lamprophiidae - Malpolon monspessulanus, Psammophis schokari, Psammophis subtaeniatus, Rhamphiophis oxyrhynchus; and Viperidae – Bitis atropos, Pseudocerastes urarachnoides, Tropidolaeumus subannulatus, Vipera transcaucasiana. These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP/BNP tailed condition. Also shown was that the de novo evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances in procoagulant venoms where kunitz peptides were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within Bungarus venoms. Conclusions We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator–prey evolutionary arms races, ascertain differential clinical pathologies, as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline.

The aim of this work was to evaluate diuretic activity of the ethanol extract of Euphorbia hirta leaves and elucidate the possible mechanism of its action. The diuretic activity was studied on male albino rats in comparison to furosemide as a standard drug. Two doses of E. hirta extract (300 and 600 mg/kg) were administered and the urinary volume and electrolyte (Na+, K+) concentrations were measured. Results showed that administration of the ethanol extract of E. hirta led to significantly increased urinary volume and excretion of urinary electrolytes such as sodium, potassium and chloride in 24 h urine compared to that for normal animals. Among the two selected doses, 600 mg/kg body weight exhibited higher diuretic activity level than 300 mg/kg dose. Although both these levels were statistically significant when compared to control in respect of all parameters, these levels were lower compared to the standard drug. Hence, the ethanol extract of E. hirta exhibited a dose dependent diuretic activity. Upon the isolation and identification of active compounds from E. hirta ethanol extract, it was found that lupeol and quercetin were the major constituents responsible for the diuretic activity in rats. The present study confirmed validity of the ethnopharmacological use of E. hirta as a diuretic agent under experimental conditions studied. [ABSTRACT FROM AUTHOR]

Pavetta crassipes is a plant used in the treatment of hypertension. The aim of the study was to evaluate the diuretic potential of aqueous leaf extract of P. crassipes in rats. Four hours and twenty-four hours diuretic and natriuretic activities of 125, 250 and 500 mg/kg aqueous leaf extract of P. crassipes were determined with distilled water and 10 mg/kg furosemide acting as negative and positive controls respectively in rats. Urine output was measured using graduated and transparent tubes on rat's metabolic cages, while urinary sodium, potassium, and chloride assays were carried out using a spectrophotometer and standard test kits. P. crassipes extract at 125, 250 and 500 mg/kg lacks diuretic activity at four hours but showed diuretic activity at 24 hours when compared with furosemide. The aqueous extract (125, 250 and 500 mg/kg) significantly increased urine output when compared with the distilled water group at 24 hours (p=0.03, p=0.04, and p=0.01, respectively). All the tested doses of the extract had a lower four hours natriuretic value when compared with furosemide, but higher natriuretic values at 24 hours. The extract increased the excretion of sodium (Na+), potassium (K+) and chloride (Cl-). The aqueous leaf extract of P. crassipes increased urine output in rats, with a late onset of diuresis and a good natriuretic activity at 24 hours, suggesting it as a possible good diuretic agent. [ABSTRACT FROM AUTHOR]

Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E metabolism and biological activities of vitamin E metabolites. Research has established that tocopherols and tocotrienols are metabolized via ω-hydroxylase (CYP4F2)-initiated side chain oxidation to form 13′-hydroxychromanol and 13′-carobyxychromanol (13′-COOH). 13′-COOHs are further metabolized via β-oxidation and sulfation to intermediate carboxychromanols, terminal metabolite carboxyethyl-hydroxychroman (CEHC), and sulfated analogs. Animal and human studies show that γ-, δ-tocopherol and tocotrienols are more extensively metabolized than α-tocopherol (αT), as indicated by higher formation of CEHCs and 13′-COOHs from non-αT forms than those from αT. 13′-COOHs are shown to be inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase and much stronger than CEHCs for these activities. 13′-COOHs inhibit cancer cell growth, modulate cellular lipids and activate peroxisome proliferator-activated receptor-γ and pregnane X receptor. Consistent with mechanistic findings, αT-13′-COOH or δTE-13′-COOH, respective metabolites of αT or δ-tocotrienol, show anti-inflammatory and cancer-preventive effects, modulates the gut microbiota and prevents β-amyloid formation in mice. Therefore, 13′-COOHs are a new class of bioactive compounds with anti-inflammatory and anti-cancer activities and potentially capable of modulating lipid and drug metabolism. Based on the existing evidence, this author proposes that metabolites may contribute to disease-preventing effects of γ-, δ-tocopherol and tocotrienols. The role of metabolites in αT's actions may be somewhat limited considering controlled metabolism of αT because of its association with tocopherol-transport protein and less catabolism by CYP4F2 than other vitamin E forms. [Display omitted] • Vitamin E tocopherols and tocotrienols are metabolized by CYP4F2 to form metabolites including 13'-COOHs and CEHCs. • Gamma-, delta-tocopherols and tocotrienols are more extensively metabolized than alpha-tocopherol. • 13'-COOHs are inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase, inhibit cancer cell growth, and activate PPAR and PXR. • 13'-COOHs are capable of anti-inflammation, anti-cancer and modulating lipid and drug metabolism. • Metabolites may contribute to bioactivities of gamma- or delta-tocopherol and tocotrienols. [ABSTRACT FROM AUTHOR]

Background: The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom or mucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Results: Transcriptomes were constructed for the following families and species: Colubridae - Helicops leopardinus, Heterodon nasicus, Rhabdophis subminiatus; Homalopsidae – Homalopsis buccata; Lamprophiidae - Malpolon monspessulanus, Psammophis schokari, Psammophis subtaeniatus, Rhamphiophis oxyrhynchus; and Viperidae – Bitis atropos, Pseudocerastes urarachnoides, Tropidolaeumus subannulatus, Vipera transcaucasiana. These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP/BNP tailed condition. Also shown was that the de novo evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances in procoagulant venoms where kunitz peptides were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within Bungarus venoms. Conclusions: We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator–prey evolutionary arms races, ascertain differential clinical pathologies, as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline. [ABSTRACT FROM AUTHOR]

Background and aimsTo investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP).Methods and resultsAs many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and

Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and collecting duct. Amiloride is indicated in oedematous states, and for potassium conservation adjunctive to thiazide or loop diuretics for hypertension, congestive heart failure and hepatic cirrhosis with ascites. Historical studies on its use in hypertension were poorly controlled and there is insufficient data on dose-response. It is clearly highly effective in combination with thiazide diuretics where it counteracts the adverse metabolic effects of the thiazides and its use in the Medical Research Council Trial of Older Hypertensive Patients, demonstrated convincing outcome benefits on stroke and coronary events. Recently it has been shown to be as effective as spironolactone in resistant hypertension but there is a real need to establish its potential role in the much larger number of patients with mild to moderate hypertension in whom there is a paucity of information with amiloride particularly across an extended dose range. [ABSTRACT FROM AUTHOR]

Background 8‐Aminoguanosine and 8‐aminoguanine are K+‐sparing natriuretics that increase glucose excretion. Most effects of 8‐aminoguanosine are due to its metabolism to 8‐aminoguanine. However, the mechanism by which 8‐aminoguanine affects renal function is unknown and is the focus of this investigation. Methods and Results Because 8‐aminoguanine has structural similarities with inhibitors of the epithelial sodium channel (ENaC), Na+/H+ exchangers, and adenosine A1 receptors, we examined the effects of 8‐aminoguanine on ENaC activity in mouse collecting duct cells, on intracellular pH of human proximal tubular epithelial cells, on responses to a selective A1‐receptor agonist in vivo, and on renal excretory function in A1‐receptor knockout rats. These experiments showed that 8‐aminoguanine did not block ENaC, Na+/H+ exchangers, or A1 receptors. Because Rac1 enhances activity of mineralocorticoid receptors and some guanosine analogues inhibit Rac1, we examined the effects of 8‐aminoguanine on Rac1 activity in mouse collecting duct cells. Rac1 activity was significantly inhibited by 8‐aminoguanine. Because in vitro 8‐aminoguanine is a purine nucleoside phosphorylase (PNPase) inhibitor, we examined the effects of a natriuretic dose of 8‐aminoguanine on urinary excretion of PNPase substrates and products. 8‐Aminoguanine increased and decreased, respectively, urinary excretion of PNPase substrates and products. Next we compared in rats the renal effects of intravenous doses of 9‐deazaguanine (PNPase inhibitor) versus 8‐aminoguanine. 8‐Aminoguanine and 9‐deazaguanine induced similar increases in urinary Na+ and glucose excretion, yet only 8‐aminoguanine reduced K+ excretion. Nsc23766 (Rac1 inhibitor) mimicked the effects of 8‐aminoguanine on K+ excretion. Conclusions 8‐Aminoguanine increases Na+ and glucose excretion by blocking PNPase and decreases K+ excretion by inhibiting Rac1.

Although present in the leaves of Mimosa bimucronata (DC.) and many other medicinal plants commonly used to augment urinary volume excretion, the effects of gallic acid as a diuretic agent remain to be studied. Wistar rats were orally treated with vehicle, hydrochlorothiazide, or gallic acid. The effects of gallic acid in the presence of hydrochlorothiazide, furosemide, amiloride, L-NAME, atropine, and indomethacin were also investigated. Diuretic index, pH, conductivity, and electrolyte excretion were evaluated at the end of the experiment (after 8 or 24 h). Gallic acid induced diuretic and saluretic (Na+ and Cl−) effects, without interfering with K+ excretion, when orally given to female and male rats at a dose of 3 mg/kg. These effects were associated with increased creatinine and conductivity values while pH was unaffected by any of the treatments. Plasma Na+, K+, and Cl− levels were not affected by any of the acute treatments. The combination with hydrochlorothiazide or furosemide was unable to intensify the effects of gallic acid when compared with the response obtained with each drug alone. On the other hand, the treatment with amiloride plus gallic acid amplified both diuresis and saluresis, besides to a marked potassium-sparing effect. Its diuretic action was significantly prevented in the presence of indomethacin, a cyclooxygenase inhibitor, but not with the pretreatments with L-NAME or atropine. Although several biological activities have already been described for gallic acid, this is the first study demonstrating its potential as a diuretic agent. [ABSTRACT FROM AUTHOR]

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues. [ABSTRACT FROM AUTHOR]

Background: Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects., Objective: This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity., Methods: Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well., Conclusion: Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To evaluate the diuretic activity and acute toxicity profile of the crude aqueous extract of Achyranthes aspera using animal models. Methods: Albino rats of either sex were divided into five groups (six animals in each group). The control group received normal saline (10 ml/kg), the reference group received furosemide (10 mg/kg) and the test groups were administered different doses of the crude aqueous extract (10, 30 and 50 mg/kg) by intra-peritoneal route, respectively. At the end of 6 h, urine was collected and total volume of urine excreted by each rat was expressed as ml/6 h/100 g of body weight. pH of fresh urine samples, concentration of urinary sodium and potassium ions, Lipschitz value, diuretic index, saliuretic index and Na+/K+ ratio were also calculated to make comparison among the groups. The acute toxicity of the crude extract was assessed in Albino mice. Results: The findings demonstrated that the crude aqueous extract of the plant showed significant diuretic (p < 0.001), natriuretic (p < 0.001) and kaliuretic (p < 0.001) effects. However, during the course of the study, urinary pH remained unchanged. The diuretic index values for the test groups (III, IV & V) were 2.3, 2.6 and 3.1, respectively. Lipschitz values showed that, at the dose of 50 mg/kg, the crude extract showed 46% of diuretic activity as compared with furosemide. No toxic effects were observed among Albino mice even at a higher dose of 3000 mg/kg. Conclusion: The crude extract of Achyranthes aspera increases the urine volume and concentration of urinary electrolytes in a dose-dependent manner. Therefore, this plant has a diuretic potential. However, future studies should focus on isolating the phytochemical component(s) responsible for diuresis. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effect of crude aqueous extract of Boswellia serrata Roxb. oleo gum on urinary electrolytes, pH and diuretic activity in normal albino rats. Moreover, acute toxicity of the gum extract was assessed using mice. Albino rats were divided into five groups. Control group received normal saline (10 mg/kg), reference group received furosemide (10 mg/kg) and test groups were given different doses of crude extract (10, 30 and 50 mg/kg) by intra-peritoneal route, respectively. The Graph Pad Prism was used for the statistical analysis and p < 0.05 was considered statistically significant. Significant diuretic, kaliuretic and natriuretic effects were observed in the treated groups in a dose dependent manner. Diuretic index showed good diuretic activity of the crude extract. Lipschitz values indicated that the crude extract, at the dose of 50 mg/kg, showed 44 % diuretic activity compared to the reference drug. No lethal effects were observed among albino mice even at the higher dose of 3000 mg/kg. It is concluded that aqueous extract of Boswellia serrata oleo gum, at the dose of 50 mg/kg showed significant effects on urinary volume and concentration of urinary electrolytes with no signs of toxicity. [ABSTRACT FROM AUTHOR]

In vivo, 8‐nitroguanosine, an endogenous biomolecule produced by peroxynitrite chemistry, is converted to 8‐aminoguanine via two biochemical pathways. 8‐Aminoguanine levels are increased in Dahl salt‐sensitive rats. [Display omitted] 8-Aminoguanine exerts natriuretic and antihypertensive activity. Whether and how "free" 8-aminoguanine exists in vivo is unclear. Because 8-nitroguanosine is naturally occurring, we tested the hypothesis that 8-aminoguanine can arise from: pathway 1 , 8-nitroguanosine → 8-aminoguanosine → 8-aminoguanine; and pathway 2 , 8-nitroguanosine → 8-nitroguanine → 8-aminoguanine. 8-Aminoguanine biosynthesis was explored in rats using renal microdialysis, mass spectrometry and enzyme kinetics. In Sprague-Dawley rats, 8-nitroguanosine infusions increased kidney levels of 8-nitroguanine, 8-aminoguanosine and 8-aminoguanine; 8-nitroguanine infusions increased 8-aminoguanine. Purine nucleoside phosphorylase (PNPase) converted 8-nitroguanosine to 8-nitroguanine and 8-aminoguanosine to 8-aminoguanine. Forodesine (PNPase inhibitor) reduced metabolism of 8-nitroguanosine by pathway 2 and shunted metabolism of 8-nitroguanosine to 8-aminoguanosine. In Dahl salt-sensitive rats, 8-nitroguanosine infusions increased kidney levels of 8-nitroguanine, 8-aminoguanosine and 8-aminoguanine. These results indicate that both pathways 1 and 2 participate in the biosynthesis of 8-aminoguanine in Sprague-Dawley and Dahl rats. Endogenous 8-aminoguanine in kidneys and urine were elevated many-fold in Dahl, compared to Sprague-Dawley, rats. The increased levels of 8-aminoguanine in Dahl rats were not due to alterations in pathways 1 and 2 but were associated with increased urine levels of endogenous 8-nitroguanosine suggesting that the "upstream" production of 8-nitroguanosine was increased in Dahl rats. Dahl rats are known to have high levels of peroxynitrite, and peroxynitrite is known to nitrate guanosine in biomolecules. Here we confirm that a peroxynitrite donor increases kidney levels of 8-aminoguanine. 8-Aminoguanine occurs naturally via two distinct pathways and kidney levels of 8-aminoguanine are increased in Dahl rats, likely due to increased production of 8-nitroguanosine, a by-product of peroxynitrite chemistry. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diuretic effect and acute toxicity of the crude aqueous extract of Trianthema portulacastrum in a rat model. Method: Albino rats were divided into five groups. Control group received normal saline (10 mg/kg), reference group received furosemide (10 mg/kg) and test groups were given different doses of crude extract (10, 30 and 50 mg/kg) by intraperitoneal route. Urine was collected and the total volume of urine excreted was expressed as ml/6 hr/100 g body weight. Diuretic index and Lipschitz values were also calculated to make comparison with normal saline and furosemide treated groups, respectively. Results: Significant diuretic (p < 0.001), kaliuretic (p < 0.001) and natriuretic (p < 0.001) effects were observed in treated groups in a dose-dependent manner. Urinary pH remained mostly unchanged during the course of the study. Diuretic index showed good diuretic activity of the crude extract. Lipschitz values indicated that the crude extract at the dose of 50 mg/kg exhibited 79 % diuretic activity compared with that of the reference, furosemide. No lethal effects were observed among albino mice even at the high dose of 3000 mg/kg. Conclusion: The extract of Trianthema portulacastrum, particularly, at the dose of 50 mg/kg significantly increased the urinary volume and concentration of urinary electrolytes with no signs of toxicity and therefore, is a potential diuretic. Further studies, however, are required to isolate the active constituents. [ABSTRACT FROM AUTHOR]

Heart failure is an important public health problem that is increasing in prevalence throughout the world. Not only is this condition common, but it is associated with significant morbidity and mortality as well as high costs to medical care systems. Vasodilator drugs help unload the heart and may have other effects that could benefit heart failure patients. Consequently, they have emerged as an important therapeutic approach for patients with this condition. Novel vasodilator therapies that are currently in development target new pathways, potentially giving clinicians alternate options for improving outcomes in this vulnerable population. This review focuses on investigational drugs that have the ability to dilate blood vessels amongst their therapeutic properties. These drugs include the natriuretic peptides that activate particulate guanylate cyclase, the novel agent cinaciguat that activates the soluble guanylate cyclase system, and finally a recombinant form of the naturally occurring vasodilating agent relaxin, a hormone that mediates many of the changes that allows the cardiovascular system to successfully adapt to pregnancy. [ABSTRACT FROM AUTHOR]

Copyright of Les Cahiers de l'Année Gérontologique is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Aim of the study: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. Material and methods: Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25–100mg/kg) and isoquercitrin (5–10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na+) and potassium (K+) electrolytes were measured in the urine of saline-loaded animals. Results: The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na+. Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na+ and K+ had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. Conclusion: This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin. [Copyright &y& Elsevier]

Abstract: Isatin, an endogenous indole compound, prevents atrial natriuretic peptide (ANP) from signaling through its cell-surface receptor, NPRA. Allergic airway inflammation has been linked to natriuretic peptide signaling and blocking this signaling axis in the lung prevents allergen-induced pathology. In this study we encapsulated isatin in chitosan nanoparticles and tested them in a mouse model of allergic asthma by intranasal delivery to the lung. Isatin nanocapsules reduced lung pathology by blocking ANP signaling, but surprisingly also by reducing the expression of NPRA. Ovalbumin-allergic mice were treated intranasally with isatin-containing chitosan nanocapsules either before or after allergen challenge, and lung function, cytokine levels, histopathology and cellular infiltration were determined. ANP activity was quantitated by measuring changes in intracellular cyclic GMP and changes in NPRA levels were determined. For comparison with isatin''s effects, the expression of the receptor was inhibited with small interfering RNA against NPRA mRNA. Isatin nanocapsules administered locally to the lung reduced cGMP production and NPRA expression and protected allergic mice from airway hyperreactivity and lung inflammation when given either before or after allergen challenge. Leukocyte infiltration was reduced and lung cytokine profiles showed a repolarization from a Th2-like to a Th1-like phenotype. Isatin nanocapsules administered locally to the lung inhibit NPRA signaling but also are capable of lowering the expression of NPRA, thus effectively reducing inflammation in a mouse model of allergic asthma. Pharmacological intervention to reduce NPRA activity through the inflammatory natriuretic peptide axis in the lung may be a useful adjunct therapy for treating lung disease. [Copyright &y& Elsevier]

Aims. This study was performed to evaluate the relationship between three different natriuretic peptides and left ventricular mass, function and diameter, and kidney function in patients with hypertension. Methods. One hundred and thirty-nine patients with moderate hypertension were consecutively included. N-terminal brain natriuretic peptide (Nt-BNP), brain natriuretic peptide (BNP) and N-terminal pro-atrial natriuretic peptide (Nt-ANP) were analyzed. Cardiac remodeling was assessed by echocardiography (UCG) and glomerular filtration was estimated by cystatin C. Results. Patients were stratified into four groups with regard to the extent of cardiac remodeling: (1) no remodeling; (2) one of left ventricular hypertrophy, left ventricular dysfunction or left ventricular dilatation; (3) two of above and (4) all three parameters. All peptides differed significantly between the groups (all p<0.001), with a continuous stepwise increase from groups 1 through 4. Receiver operating characteristic analysis showed equal diagnostic performances for the detection of any cardiac abnormalities for Nt-BNP [area under curve, AUC=0.63 (0.52-0.75), p=0.026] and BNP [AUC=0.64 (0.53-0.76), p=0.019], both, however superior to Nt-ANP [AUC=0.59 (0.47-0.70), p=0.139]. In multivariable linear regression analysis, all three indicators of cardiac remodeling were independently correlated with ln Nt-BNP and ln BNP, whereas only left ventricular diameter was independently correlated with ln Nt-ANP. Conclusions. Natriuretic peptide levels increased with increasing number of markers of cardiac remodeling. Nt-BNP and BNP are useful to discriminate between patients with regard to cardiac remodeling and might be considered a screening tool in order select patients eligible for further examination with UCG examination. [ABSTRACT FROM AUTHOR]

Abstract: Since the first report of their natriuretic effect on mammalian kidneys the relative influences of natriuretic peptides (NPs) on volume and salt regulation in vertebrates have been debated. As marine osmoconformers, with plasma ionic concentrations similar to seawater, the actions of NPs on hagfishes may provide information on their primordial role. A synthetic natriuretic peptide derived from Eptatretus burgeri (hNP) increased urine production rates in E. cirrhatus at 3×10−8 M. It also contracted afferent branchial and segmental arteries at low concentrations (1×10−10 M) and relaxed them at 3×10−8 M. Thus, hNP has a renal effect and at higher concentrations causes vascular relaxation suggesting a role in volume regulation and the prevention of cardiac overloading. Rat ANP (rANP) stimulated sodium efflux from both isolated, perfused gill pouches and the whole animal. rANP also reduced subcutaneous sinus haematocrit relative to that in the ventral aorta, which is consistent with a vasodilatory role. [Copyright &y& Elsevier]

Abstract: There is increasing interest in the health and wellness benefits of herbs and botanicals. This is with good reason as they might offer a natural safeguard against the development of certain conditions and be a putative treatment for some diseases. One such area may be the lowering of blood pressure in those where it is elevated (i.e., hypertension). One class of clinical medicines used to lower blood pressure are known as diuretics and work by increasing the excretion of urine from the body as well as the amount of sodium in urine. There are a growing number of studies purporting diuretic effects with traditional medicines. The aim of this article was to review these studies and identify which extracts promote diuresis (which we assessed on terms of urine excreted and urinary sodium excretion) and also to identify the research needs in this area. We identified a number of species and genuses reporting diuretic effects. Of these, the most promising, at the present time, are the species Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum and Spergularia purpurea, and species from the genuses Cucumis (Cucumis melo and Cucumis trigonus), Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum), Lepidium (Lepidium latifolium and Lepidium sativum), Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus) and Sambucus (Sambucus mexicana and Sambucus nigra). However, there the number of studies is limited and we recommend that further studies be conducted to confirm reported effects. Such evidence is needed to provide scientific credence to the folklore use of traditional medicines and even be helpful in the development of future medicines, treatments and treatment guidelines. [Copyright &y& Elsevier]

Abstract: This study examined the effect of transfer to increased environmental salinity on the circulating levels of angiotensin II (ANG II), C-type natriuretic peptide (CNP), and arginine vasotocin (AVT) in the euryhaline elasmobranch, Carcharhinus leucas. Plasma levels of ANG II and CNP were significantly increased in C. leucas chronically acclimated to seawater (SW) in comparison to freshwater (FW) acclimated fish. There was no difference in plasma AVT levels. Acute transfer of FW fish to 75% SW induced an increase in plasma ANG II levels within 12h, and subsequent transfer from 75 to 100% SW further increased plasma ANG II levels at both 24 and 72h. No change in plasma CNP was observed during acute transfer to increased salinity. However, a significant increase in plasma AVT levels was observed following 96h in 75% SW and 24h in 100% SW. In chronically SW acclimated C. leucas plasma osmolality, sodium, chloride, and urea were all significantly higher than FW acclimated fish but there was no difference in haematocrit. Acute transfer of C. leucas to 75% SW induced a significant increase in plasma osmolality, sodium and urea concentrations within 96h of transfer. Subsequent transfer from 75 to 100% SW induced a further increase in these variables within 24h in addition to a significant increase in plasma chloride above control levels. Haematocrit did not differ between the experimental and control groups throughout the acute study. Circulating levels of ANG II were significantly correlated to plasma, sodium, chloride, and urea concentrations during acclimation to SW. Conversely, circulating levels of CNP and AVT did not correlate to plasma osmolytes, however, CNP was significantly correlated to haematocrit during acclimation to seawater. [Copyright &y& Elsevier]

Brain natriuretic peptide (BNP) is a cardiac neurohormone of increasing interest over recent years, with research applications expanding at a rapid rate and new data published on a monthly basis. Initially developed as a diagnostic aid for those with acute shortness of breath, clinical applications are now increasing, and this article reviews these clinical applications of BNP and the evidence for effectiveness of the synthetic BNP analogue nesiritide. [ABSTRACT FROM PUBLISHER]

Evidence suggests that adrenomedullin (AM) plays a role in the pathophysiology of heart failure. Circulating concentrations of AM are elevated in cardiovascular disease in proportion to the severity of cardiac and hemodynamic impairment. Raised plasma AM levels following acute cardiac injury and in heart failure provide prognostic information on adverse outcomes. In heart failure, elevated circulating AM also identifies patients likely to receive long-term benefit from inclusion of additional anti-failure therapy (carvedilol). Administration of AM in experimental and human heart failure induces reductions in arterial pressure and cardiac filling pressures, and improves cardiac output, in association with inhibition of plasma aldosterone (despite increased renin release) and sustained (or augmented) renal glomerular filtration and sodium excretion. Furthermore, AM in combination with other therapies (angiotensin-converting enzyme inhibition and augmentation of the natriuretic peptides) results in hemodynamic and renal benefits greater than those achieved by the agents separately. Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease. [Copyright &y& Elsevier]

Unlabelled: The purpose of this study was to investigate the changes in plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD) during transcatheter closure of defects. The plasma concentrations of ANP and BNP were obtained from 14 patients with ASD at before closure, and at 5 min, 24 h, 1 mo and 3 mo after transcatheter ASD closure using an Amplatzer septal occluder. Ten healthy children aged 6-18 y were studied as controls. All ASDs were successfully closed. Compared with control values (mean +/- SD, 17 +/- 6.8 ng 1(-1), ANP concentrations before closure were significantly elevated (24 +/- 9.8ng 1(-1), p < 0.05). ANP concentrations increased significantly at 5 min after closure (34 +/- 18 ng 1(-1), p < 0.05) compared with preclosure concentrations. At 24 h after closure, the concentrations decreased to values not different from control values (19 +/- 11 ng 1(-1), p = ns). BNP levels before closure (19 +/- 9.9 ng 1(-1) were also elevated significantly compared with control values (12 +/- 4.9ng 1(-1), p < 0.05). BNP concentrations increased significantly at 5 min after closure (23 +/- 14 ng 1(-1), p < 0.05) compared with preclosure concentrations. ANP values at 24 h were lower than at 5 min after closure, whereas BNP values were higher (32 +/- 11 ng 1(-1), p < 0.05). As with ANP, the concentrations gradually decreased to values not different from control values at 3 mo after the procedure (12 +/- 6.3 ng 1(-1), p = ns).Conclusion: Plasma concentrations of ANP and BNP may become effective markers for evaluating changes in cardiac load after transcatheter ASD closure. [ABSTRACT FROM AUTHOR]

Furosemide and inulin were given simultaneously by intravenous infusion to nine subjects over 2 h. The concentrations of sodium and of the two drugs in serum (free and protein bound) and in urine were followed during the infusion. In 6 male subjects the investigation was repeated after 3 days of oral treatment with probenecid 500 mg twice daily. Probenecid reduced the average ratio furosemide clearance/inulin clearance from 0.92 to 0.44. In experiments in which no probenecid had been given an average of 2% of the furosemide in urine was excreted by glomerular filtration. In vitro studies showed that the protein binding of furosemide was decreased in the presence of probenecid. The displacing effect of probenecid was confirmed in vivo, and during probenecid treatment glomerular filtration produced an average of 8% of the furosemide excreted by the kidney. The fraction of furosemide excreted by tubular secretion decreased during probenecid treatment from 98.0±0.6% to 91.7±5.6% ( p<0.05). Prior to administration of probenecid, the fraction of the filtered sodium recovered from the urine during furosemide administration was 24.7%. Probenecid reduced that fraction to 21.0% ( p<0.05). The excretion rate of furosemide appeared to be a better predictor of the natriuretic effect than its plasma concentration. Probenecid caused a significant change ( p<0.05) in the regression line relating the log plasma concentration to the natriuretic effect, but it had no effect on the regression line relating the log urinary excretion rate of furosemide to its natriuretic effect. Although the decrease in the furosemide excretion rate during probenecid treatment averaged 25%, the sodium excretion rate was reduced by less than 15%. It is suggested that the natriuretic effect of furosemide is more pronounced if the furosemide molecules enter the tubular lumen at a more proximal level, and it is strongest if they do so by filtration through the glomerulus. [ABSTRACT FROM AUTHOR]

The maintenance of blood volume during exercise, especially in a hot environment, is of major importance for continued performance. In order to investigate the relationships between exercise, type and amount of fluid intake and the degree of acclimatization to heat stress and on responses of arginine vasopressin (AVP), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we studied 24 soldiers during and after jogging/walking exercise both before and after acclimatization to field training at [mean (SE)] 40 (0.7) °C and 32 (3)% relative humidity. The running exercise was carried out under three conditions, i.e., (1) without any fluid intake, (2) with intake of water or (3) with intake of a dextrose/electrolyte solution. Venous blood samples were drawn before exercise, at the end of exercise and at 15 min and 60 min afterwards. Acclimatization resulted in significant losses of body mass, total body water, plasma volume, ANP and increases in plasma osmolality, packed cell volume and AVP at rest but without any significant changes in BNP. During exercise with no fluid intake, there was a significant rise in plasma osmolality, Na+ and AVP, but no significant alterations in plasma ANP and BNP were observed. When subjects ingested water or dextrose/electrolyte solution during exercise, ANP rose by 234% and 431% respectively and BNP rose by 398% and 583% respectively without any significant increase in AVP. The results suggest that, during acclimatization, the subjects became slightly dehydrated. Alterations in response to changes in body water status appear to be greater for AVP than ANP or BNP at rest. During exercise in the heat ANP and BNP may play complementary roles. [ABSTRACT FROM AUTHOR]

The renal effects of bumetanide, a new diuretic chemically related to furosemide, have been studied in four young healthy volunteers during dehydration and water diuresis. Bumetanide produced a considerable diuresis due mainly to an increase in osmotic clearance. The peak urinary volume amounted to about 1/3 of the filtered volume, indicating an effect of the drug on the proximal tubule. Free water clearance was not significantly affected. During dehydration, with its superimposed osmotic diuresis, bumetanide diminished the concentrating power of the kidney so that an almost isotonic urine was produced. This result implied an additional effect on the distal parts of the nephron and it may represent partial blockade of sodium reabsorption in the ascending limb of the loop of Henle. [ABSTRACT FROM AUTHOR]