Effect of sympathetic and angiotensin-aldosterone systems on renal salt conservation in the rat

1997 ◽  
Vol 272 (4) ◽  
pp. F538-F544 ◽  
Author(s):  
U. Honrath ◽  
A. T. Veress ◽  
C. K. Chong ◽  
H. Sonnenberg
Keyword(s):  
Control Group ◽  
Dietary Salt ◽  
Drug Induced ◽  
Efferent Nerve ◽  
Salt Diet ◽  
Salt Excretion ◽  
Losartan Group ◽  
Chloride Excretion ◽  
Salt Depletion ◽  
6 Hydroxydopamine

During dietary salt deprivation, the sympathetic nervous system and the angiotensin-aldosterone system are stimulated. Both systems are thought to be essential for maximal salt conservation by the kidney. To study their relative contributions, we produced negative salt balance in rats by intraperitoneal injection of furosemide, followed by a low-salt diet (<0.008% NaCl). In a 1-wk metabolic study, the animals were unable to replace the drug-induced salt deficit. Six groups of rats were studied. A control group established baseline function, a second group of 6-hydroxydopamine (OHDA) rats were treated with OHDA to destroy sympathetic efferent nerve terminals, and a third group (losartan) were treated with the angiotensin-receptor antagonist losartan. The influence of catecholamines and aldosterone released from the adrenal gland was studied in a further three groups. Rats were sham-adrenalectomized (sham), subjected to bilateral adrenal enucleation (Enuc) to eliminate catecholamine secretion, or were bilaterally adrenalectomized (Adx), eliminating both catecholamine and corticosteroid release. Dexamethasone was used as glucocorticoid replacement in this group. Steady-state urinary salt excretion was not different between control and OHDA rats. The losartan group showed significantly increased sodium but not chloride excretion. Surprisingly, there were no differences in salt excretion among sham, Enuc, and Adx groups. We conclude that, during a state of chronic salt depletion, renal mechanism(s) independent of neuronally released or systemically circulating catecholamines or of adrenally released aldosterone can ensure maximal salt conservation by the kidney. Although our data show that losartan increased sodium excretion under these conditions, we suggest that the losartan effect can be explained by a reduction of bicarbonate reabsorption, obligating simultaneous excretion of the cation.

Abstract 11: Single Cell Eccite-seq Analysis Reveal An Important Role Of Monocyte-specific Nlrp3 Inflammasome For Salt-sensitivity Of Hypertension In Humans

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ashley L Pitzer ◽  
Melis Sahinoz ◽  
Michael Raddatz ◽  
Celestine Wanjalla ◽  
Suman Pakala ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Flow Cytometry ◽  
Nlrp3 Inflammasome ◽  
Immune Cell ◽  
Cell Types ◽  
Salt Sensitivity ◽  
Dietary Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Salt Depletion

Salt sensitivity of blood pressure is an independent predictor of death due to cardiovascular events. Diagnosis of salt-sensitivity is not feasible in the clinic, making it difficult to investigate therapeutic strategies. We hypothesized that NLRP3-inflammasome and IL-1β production in monocytes plays a role in salt-sensitive hypertension. We phenotyped salt-sensitivity of blood pressure using an acute inpatient Weinberger protocol of an isocaloric high salt diet and rapid intravenous salt-loading, followed by low salt diet and furosemide-induced salt-depletion. Ambulatory blood pressure was continuously monitored and averaged for the days of salt-loading and salt-depletion. Blood samples were obtained at baseline, salt-loading, and after salt-depletion. Median age was 54 years (44-55), 3 of the 5 subjects were female, screening systolic blood pressure was 140 mmHg (134-148), diastolic blood pressure was 88 mmHg (84-99), and BMI was 35 kg/m 2 (30-39). Using cell hashing and ECCITE-seq analysis, we profiled transcriptomes in multiple immune cell types using antibody-derived tags (ADTs). UMAP clustering of different cell types were identified by ADTs including monocyte markers CD14 and CD16. Interestingly, UMAP visualization of CD14+ and CD16+ clusters indicated a greater decrease in CD14+ clusters after salt-depletion in the salt-resistant subjects than the salt-sensitive; however the salt-sensitive subjects had a greater decrease in CD16+ clusters than the salt-resistant group after both salt-loading and salt-depletion. These data were confirmed using flow cytometry. Unlike in salt-resistant participants, we found that within monocyte clusters, salt-sensitivity was associated with down regulation of the inflammasome components NLRP3 (0.386 ± 1.18 vs. 0.197 ± 0.778) and IL-1β (0.858 ± 2.32 vs. 0.159 ± 0.925) following salt-depletion. Using flow cytometry, we found Δ% isoLG+ CD14+/CD16+ monocytes correlated with salt-sensitivity of blood pressure (r=0.88, 95% CI, p=0.05). These results suggest that the inflammasome and monocyte activation are dynamically regulated by dietary salt in vivo and can serve as a potential diagnostic biomarker for salt-sensitivity of blood pressure.

Renal resistance to ANF in salt-depleted rats is independent of sympathetic or ANG-aldosterone systems

1997 ◽  
Vol 272 (4) ◽  
pp. F545-F550
Author(s):  
A. T. Veress ◽  
U. Honrath ◽  
C. K. Chong ◽  
H. Sonnenberg
Keyword(s):  
Renal Perfusion ◽  
Compensatory Mechanism ◽  
Salt Diet ◽  
Low Salt ◽  
The Face ◽  
Order Of Magnitude ◽  
Salt Depletion ◽  
Natriuretic Effect ◽  
6 Hydroxydopamine ◽  
Postganglionic Nerve

Chronic salt depletion was used as a model to study the mechanism of renal resistance to the natriuretic effect of atrial natriuretic factor (ANF). Rats were pretreated with furosemide and placed on a low-salt diet (<0.008% NaCl) for 1 wk before a clearance experiment. Compared with animals on a normal salt diet (0.4% NaCl), the natriuretic reponse to ANF administration was reduced by one order of magnitude and was quantitatively trivial. To assess the influence of the sympathoadrenergic system, different groups of rats were either subjected to acute unilateral renal denervation, to chronic adrenal enucleation to reduce circulating catecholamines, or to pretreatment with 6-hydroxydopamine (OHDA) to destroy sympathetic postganglionic nerve endings. None of these treatments was able to fully or even partially restore ANF natriuresis. To determine whether an effect of angiotensin on the kidney prevented the response, the specific receptor antagonist losartan (DuP-753) was administered during the week prior to the experiment. This treatment also did not influence ANF resistance. Similarly, bilateral adrenalectomy 2 wk before the experiment did not affect the renal ANF resistance in salt-depleted rats. The depressed excretory response could not be explained on the basis of reduced renal perfusion pressure or glomerular filtration rate. We conclude that undetermined compensatory mechanism(s) ensures renal salt conservation in this model in the face of even supraphysiological levels of ANF.

scholarly journals Effect of Oral Losartan on Orthobiologics: Implications for Platelet-Rich Plasma and Bone Marrow Concentrate—A Rabbit Study

2020 ◽  
Vol 21 (19) ◽  
pp. 7374
Author(s):  
Gilberto Y. Nakama ◽  
Sabrina Gonzalez ◽  
Polina Matre ◽  
Xiaodong Mu ◽  
Kaitlyn E. Whitney ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteochondral Defect ◽  
Platelet Rich Plasma ◽  
Control Group ◽  
Bone Marrow Concentrate ◽  
Significant Difference ◽  
Losartan Group ◽  
Group 2 ◽  
And Control ◽  
Tgf Β1

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).

Effects of the lipase inhibitor orlistat on intake and preference for dietary fat in rats

1996 ◽  
Vol 271 (1) ◽  
pp. R48-R54 ◽  
Author(s):  
K. Ackroff ◽  
A. Sclafani
Keyword(s):  
Body Weight ◽  
Dietary Fat ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Female Rats ◽  
Control Group ◽  
Fat Intake ◽  
Fat Absorption ◽  
Drug Induced ◽  
Dietary Fat Intake

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

scholarly journals Bicyclol for the treatment of drug-induced liver injury: a propensity score matching analysis using a nationwide inpatient database

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Yongfeng Wang ◽  
Rongtao Lai ◽  
Peilan Zong ◽  
Qingling Xu ◽  
Jia Shang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Statistical Significance ◽  
Control Group ◽  
Time Interval ◽  
Potential Candidate ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Propensity Score Matching Analysis

ObjectiveTo evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database.MethodsWe retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified.ResultsThe analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups.ConclusionsBicyclol is a potential candidate for DILI.

scholarly journals Self-monitoring urinary salt excretion in adults: A novel education program for restricting dietary salt intake

2011 ◽  
Vol 2 (4) ◽  
pp. 615-618 ◽  
Author(s):  
KENICHIRO YASUTAKE ◽  
KAYOKO SAWANO ◽  
SHOKO YAMAGUCHI ◽  
HIROKO SAKAI ◽  
HATSUMI AMADERA ◽  
...  
Keyword(s):  
Education Program ◽  
Salt Intake ◽  
Dietary Salt ◽  
Self Monitoring ◽  
Dietary Salt Intake ◽  
Salt Excretion

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 79 ◽  
Author(s):  
Sergejs Isajevs ◽  
Darja Isajeva ◽  
Ulrika Beitnere ◽  
Baiba Jansone ◽  
Ivars Kalvinsh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Substantia Nigra ◽  
Rat Model ◽  
Control Group ◽  
Western Blot Assay ◽  
Neural Cell Adhesion ◽  
6 Hydroxydopamine ◽  
Cardioprotective Drug

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM). Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay. Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values. Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.

scholarly journals CYP2E1-DEPENDENT VARIATIONS IN HEPATOCYTES DAMAGE DURING TREATMENT OF TUBERCULOSIS

2019 ◽  
Vol 16 (3) ◽  
pp. 20-26
Author(s):  
L.V. Natrus ◽  
L.V. Gayova ◽  
O.O. Gorkunenko ◽  
P.A. Chernovol ◽  
M.V. Zelinska
Keyword(s):  
Gene Polymorphism ◽  
Maintenance Therapy ◽  
Genomic Dna ◽  
Clinical Laboratory ◽  
Intensive Therapy ◽  
Venous Blood ◽  
Control Group ◽  
Drug Induced ◽  
Cyp2e1 Gene ◽  
Tb Treatment

Relevance. Investigation of polymorphism in a locus of CYP2E1 as the prognostic factor of drug-induced hepatotoxicity at anti-TB therapy is significant due to the influence of CYP2E1 on drug metabolism. The objective of the investigation is to analyze the association of rs2070676 СYP2E1 gene polymorphism with drug-induced hepatotoxicity by means of the clinical-laboratory values of serum transaminases at anti-TB treatment. Materials and methods. The study involved 47 patients with drug-susceptible tuberculosis first time discovered. 58 healthy volunteers comprised a control group. Laboratory indices were determined in venous blood three times: before the treatment as baseline; in 2 months of intensive therapy (isoniazid, rifampicin, ethambutol, pyrazinamide), then in 4 months of maintenance therapy (isoniazid, rifampicin). Serum activities of enzymes ALT, AST, and GGT were measured by standard algorithm on automatic analyzer BS-300. Analysis of rs2070676 polymorphism of CYP2E1 gene was performed by polymerase chain reaction using standard PureLink® Genomic DNA Kit for Purification of Genomic DNA; Manufacturer of INVITROGEN (USA). For statistical processing, IBM SPSS Statistics 23 was applied. Results. Investigation of serum ALT and AST in patients with major genotype CYP2E1 (C/C) showed the lower baseline ALT and AST levels comparing to the control group, which might be caused by suppression of hepatocytes functions at the development of the disease. Anti-TB treatment caused an increase in ALT and AST levels comparing to the baseline in patients with major CYP2E1 (C/C) genotype. In the group with C/G polymorphism, the baseline ALT level didn’t differ much from the baseline of the control group; it showed a decrease after intensive therapy and returned back to the initial level at maintenance therapy. This might be related to the certain protective property of СYP2E1 gene polymorphism. The AST level was increased after intensive therapy (to a smaller extent than for the patients with major C/C genotype) and remained on the same level at maintenance therapy. A study of GGT showed a gradual increase regardless of genotype. Conclusion. According to the data of the experiment, the status of hepatocytes in patients with tuberculosis at baseline and during treatment was different depending on the CYP2E1 genotype. The results of the experiment indicate that the CYP2E1 gene polymorphism has a certain protecting role. It reduces the level of drug metabolites and hepatotoxicity which causes mitochondrial dysfunction.

Abstract 376: The Expression of (pro)renin Receptor is Upregulated in the Kidney by High Salt Diet and No Inhibition

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Rong Rong ◽  
Osamu Ito ◽  
Nobuyoshi Mori ◽  
Yuma Tamura ◽  
Akihiro Sakuyama ◽  
...  
Keyword(s):  
Collecting Duct ◽  
High Salt ◽  
Kidney Cortex ◽  
Control Group ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Levels ◽  
Nephron Segments ◽  
Sd Rats

The (pro)renin receptor ((P)RR)-bound (pro)renin not only causes the generation of angiotensin II via the increased enzymatic activity, it also activates the receptor’s own intracellular signaling pathways up-regulating the expression of the profibrotic proteins. To clarify the regulation of (P)RR expression, the present study examined the effects of high salt diet and nitric oxide synthase (NOS) inhibition on the (P)RR expression in the kidney. The nephron segments were isolated from male Sprague-Dawley (SD) rats by microdissection and bulk isolation technique, and the (P)RR mRNA and protein expressions were examined by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. In adiition, 5 week-old, male SD rats were randomly divided into 3 groups: a control group, a high salt diet (HS) group and a Nω-Nitro-L-arginine (L-NAME) group, and each group was treated with vehicle, high salt diet (8%, NaCl), or L-NAME (600mg/ml in drinking water), respectively. After 4 weeks, the (P)RR expression in the kidney was compared among these groups. The (P)RR mRNA was expressed in the glomerulus (Glm), the proximal convoluted and straight tubule, the cortical and medullary thick ascending limb (TAL) and collecting duct. The (P)RR protein as well as mRNA was expressed widely in the nephron segments; the preglomerular arteriole, the Glm, the proximal tubules (PT), the medullary TAL (mTAL) and inner medullary collecting duct (IMCD). Compared with the control group, the (P)RR protein levels significantly increased in the kidney cortex of both HS group and L-NAME group by 96% (p<0.01) and 506% (p<0.01) and in the inner medulla of L-NAME group by 148% (p<0.05), but did not significantly change in the outer medulla of HS group or L-NAME group. HS increased the (P)RR protein levels in the Glm and PT by 48% (p<0.05) and 39% (p<0.01), but did not affect them in other nephron segments. These results indicated that (P)RR is expressed widely in the nephron segments and that HS and NOS inhibition upregulate the (P)RR expression in the kidney, suggesting roles of (P)RR in hypertensive kidney disorder.

Reduction of liver enzyme ALT by berberis lycium in acetaminophen induced hepatic damage in mice liver.

2021 ◽  
Vol 28 (03) ◽  
pp. 287-292
Author(s):  
Furqan Ali Shah ◽  
Sabeen Shakir ◽  
Saima Rafique ◽  
Ambar Shuaib
Keyword(s):  
Experimental Study ◽  
Liver Enzyme ◽  
Plant Extract ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Drug Induced ◽  
Medical College ◽  
Herbal Plant ◽  
Berberis Lycium

Objective: The objective of this research was to study the effect of Berberis lyceum (herbal plant) in reduction of liver enzyme ALT in mice. Study Design: Quasi- experimental Study. Setting: Peshawar Medical College, Peshawar. Period: December, 2016 to May, 2017. Materials & Methods: It was an experimental study which was carried out at Peshawar Medical College Warsak Road Peshawar. Total 30 (thirty) mice were used divided in six different groups with five mice in each group. After inducing hepatotoxicity with acetaminophen in the mice, blood samples were taken and LFTs were performed to observe serum ALT values and the effects of different doses of the plant extract were evaluated. Results: The ALT levels of negative control and experimental group were compared and it was shown that ALT levels in experimental groups were 232±42.3, 143±32.5 and 62.2±18.2 whereas serum ALT value of negative control group was 571.4±123.3 which showed that ALT had been decreased by increasing the dose of plant extract. Conclusion: It was concluded that Berberis Lycium, a herbal plant has a potentially active hepato protective role in bringing serum ALT to normal. This plant can be useful in reversing the hepatotoxicity in drug induced elevation of liver enzyme ALT.

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