Hormonal regulation of salt and water excretion: a mathematical model of whole kidney function and pressure natriuresis

2014 ◽  
Vol 306 (2) ◽  
pp. F224-F248 ◽  
Author(s):  
Robert Moss ◽  
S. Randall Thomas
Keyword(s):  
Hormonal Regulation ◽  
Vascular Function ◽  
Experimental Studies ◽  
Experimental Conditions ◽  
Water Excretion ◽  
Excretory Function ◽  
Starting Point ◽  
Regulatory Effects ◽  
Pressure Natriuresis ◽  
Organ Models

We present a lumped-nephron model that explicitly represents the main features of the underlying physiology, incorporating the major hormonal regulatory effects on both tubular and vascular function, and that accurately simulates hormonal regulation of renal salt and water excretion. This is the first model to explicitly couple glomerulovascular and medullary dynamics, and it is much more detailed in structure than existing whole organ models and renal portions of multiorgan models. In contrast to previous medullary models, which have only considered the antidiuretic state, our model is able to regulate water and sodium excretion over a variety of experimental conditions in good agreement with data from experimental studies of the rat. Since the properties of the vasculature and epithelia are explicitly represented, they can be altered to simulate pathophysiological conditions and pharmacological interventions. The model serves as an appropriate starting point for simulations of physiological, pathophysiological, and pharmacological renal conditions and for exploring the relationship between the extrarenal environment and renal excretory function in physiological and pathophysiological contexts.

scholarly journals Pressure-natriuresis and -diuresis in transgenic rats harboring both human renin and human angiotensinogen genes.

1998 ◽  
Vol 9 (12) ◽  
pp. 2212-2222
Author(s):  
B Dehmel ◽  
E Mervaala ◽  
A Lippoldt ◽  
V Gross ◽  
J Bohlender ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Transgenic Rat ◽  
Water Excretion ◽  
Excretory Function ◽  
Human Renin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Pressure Natriuresis

The hypertensive double transgenic rat harboring both the human renin and human angiotensinogen genes (dTGR) offers a unique opportunity to study the human renin-angiotensin system in an experimental animal model. Since nothing is known about the control of sodium and water excretion in these rats, this study was performed to compare pressure-natriuresis relationships in hypertensive dTGR and normotensive control rats harboring only the human renin gene (hREN), in order to determine how the pressure-natriuresis relationship is reset in hypertensive dTGR. To differentiate between extrinsic and intrinsic renal mechanisms, experiments were performed with and without renal denervation, and with and without infusions of vasopressin, norepinephrine, 17-OH-corticosterone, and aldosterone. Human and rat angiotensinogen and renin mRNA expression were also determined. In hREN without controlled renal function, urine flow and sodium excretion increased from 13 to 169 microl/min per g kidney wet weight (kwt) and from 1 to 30 micromol/min per g kwt, respectively, as renal perfusion pressure was increased from 67 to 135 mmHg. Renal blood flow (RBF) and GFR ranged between 3 to 7 and 0.9 to 1.5 ml/min per g kwt. In dTGR, pressure-natriuresis-diuresis relationships were shifted approximately 40 mmHg rightward. RBF was lower in dTGR than in hREN; GFR was not different. In dTGR with neurohormonal factors controlled, RBF was decreased and pressure-natriuresis-diuresis curves were not different compared to dTGR curves without these interventions. By light microscopy, the kidneys of these 6-wk-old dTGR and hREN rats were normal and indistinguishable. Both human and rat renin and angiotensinogen mRNA were expressed in the kidneys of dTGR. The two renin mRNA were decreased in dTGR, indicating a physiologic downregulation of renin gene expression by high BP. It is concluded that the renal pressure-natriuresis mechanism is reset toward higher pressure levels in dTGR and participates in the maintenance of hypertension. The reduced excretory function in dTGR depends on hREN and human angiotensinogen gene expression and is intrinsic to the kidney as opposed to extrarenal regulators.

scholarly journals The acute pressure natriuresis response is suppressed by selective ETA receptor blockade

2021 ◽  
Author(s):  
Geoffrey Culshaw ◽  
David Binnie ◽  
Neeraj Dhaun ◽  
Patrick Hadoke ◽  
Matthew Bailey ◽  
...  
Keyword(s):  
Vascular Function ◽  
Water Retention ◽  
Salt Intake ◽  
Separate Experiment ◽  
Receptor Subtypes ◽  
Sodium Retention ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Pressure Natriuresis ◽  
Renal Tubular

Hypertension is a major risk factor for cardiovascular disease.  In a significant minority of people, it develops when salt intake is increased (salt-sensitivity).  It is not clear whether this represents impaired vascular function or disruption to the relationship between blood pressure (BP) and renal salt-handling (pressure natriuresis, PN).  Endothelin-1 (ET-1) regulates BP via ETA and ETB receptor subtypes.  Blockade of ETA receptors reduces BP, but promotes sodium retention by an unknown mechanism.  ETB blockade increases both BP and sodium retention.  We hypothesised that ETA blockade promotes sodium and water retention by suppressing PN.  We also investigated whether suppression of PN might reflect off-target ETB blockade.  Acute PN was induced by sequential arterial ligation in male Sprague Dawley rats.  Intravenous atrasentan (ETA antagonist, 5mg/kg) halved the normal increase in medullary perfusion and reduced sodium and water excretion by >60%.  This was not due to off-target ETB blockade because intravenous A-192621 (ETB antagonist, 10mg/kg) increased natriuresis by 50% without modifying medullary perfusion.  In a separate experiment in salt-loaded rats monitored by radiotelemetry, oral atrasentan reduced systolic and diastolic BP by ~10mmHg, but additional oral A-192621 reversed these effects.  Endogenous ETA stimulation has natriuretic effects mediated by renal vascular dilation while endogenous ETB stimulation in the kidney has antinatriuretic effects via renal tubular mechanisms.  Pharmacological manipulation of vascular function with ET antagonists modifies the BP set-point, but even highly selective ETA antagonists attenuate PN, which may be associated with salt and water retention.

scholarly journals Naturally Occurring Ecdysteroids in Triticum aestivum L. and Evaluation of Fenarimol as a Potential Inhibitor of Their Biosynthesis in Plants

2021 ◽  
Vol 22 (6) ◽  
pp. 2855
Author(s):  
Anna Janeczko ◽  
Jana Oklestkova ◽  
Danuše Tarkowská ◽  
Barbara Drygaś
Keyword(s):  
Triticum Aestivum ◽  
Winter Wheat ◽  
Triticum Aestivum L ◽  
Growth Conditions ◽  
Animal Kingdom ◽  
Experimental Conditions ◽  
P450 Monooxygenase ◽  
Naturally Occurring ◽  
Regulatory Effects ◽  
Potential Use

Ecdysteroids (ECs) are steroid hormones originally found in the animal kingdom where they function as insect molting hormones. Interestingly, a relatively high number of these substances can also be formed in plant cells. Moreover, ECs have certain regulatory effects on plant physiology, but their role in plants still requires further study. One of the main aims of the present study was to verify a hypothesis that fenarimol, an inhibitor of the biosynthesis of ECs in the animal kingdom, also affects the content of endogenous ECs in plants using winter wheat Triticum aestivum L. as a model plant. The levels of endogenous ECs in winter wheat, including the estimation of their changes during a course of different temperature treatments, have been determined using a sensitive analytical method based on UHPLC-MS/MS. Under our experimental conditions, four substances of EC character were detected in the tissue of interest in amounts ranging from less than 1 to over 200 pg·g−1 FW: 20-hydroxyecdysone, polypodine B, turkesterone, and isovitexirone. Among them, turkesterone was observed to be the most abundant EC and accumulated mainly in the crowns and leaves of wheat. Importantly, the level of ECs was observed to be dependent on the age of the plants, as well as on growth conditions (especially temperature). Fenarimol, an inhibitor of a cytochrome P450 monooxygenase, was shown to significantly decrease the level of naturally occurring ECs in experimental plants, which may indicate its potential use in studies related to the biosynthesis and physiological function of these substances in plants.

The Relationship of Urinary Kallikrein Activity to Renal Salt and Water Excretion

1978 ◽  
Vol 54 (1) ◽  
pp. 39-45 ◽  
Author(s):  
S. B. Levy ◽  
R. P. Frigon ◽  
R. A. Stone
Keyword(s):  
Racial Differences ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Racial Groups ◽  
Urinary Kallikrein ◽  
Experimental Conditions ◽  
Water Excretion ◽  
Water Load ◽  
Black And White ◽  
Kallikrein Activity

1. We measured urinary kallikrein (kininogenin) excretion in black and white normotensive subjects during a variety of manipulations of salt and water balance. 2. A large intravenous saline load administered while the subjects were on an unrestricted sodium diet did not significantly change urinary kallikrein activity in either racial group. 3. After several days of dietary sodium restriction both racial groups increased their urinary kallikrein activity. An intravenous water load given then further increased urinary kallikrein activity. White subjects were studied for an additional 24 h period, and urinary kallikrein activity returned to pre-water load values, indicating that the excretion of a water load in sodium-depleted subjects is associated with an increase in kallikrein excretion. 4. Black subjects excreted less kallikrein in the urine than white subjects during the initial 24 h periods of unrestricted dietary sodium intake, but there were no other significant racial differences during the other experimental conditions.

Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.

1996 ◽  
Vol 7 (12) ◽  
pp. 2694-2699
Author(s):  
M C Ortíz ◽  
L A Fortepiani ◽  
C Martínez ◽  
N M Atucha ◽  
J García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Liver Cirrhosis ◽  
Experimental Model ◽  
Systemic Blood Pressure ◽  
Arterial Hypotension ◽  
Control Group ◽  
No Production ◽  
Water Excretion ◽  
Excretory Function

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

1993 ◽  
Vol 74 (6) ◽  
pp. 2795-2800 ◽  
Author(s):  
R. Behm ◽  
H. Mewes ◽  
W. H. DeMuinck Keizer ◽  
T. Unger ◽  
R. Rettig
Keyword(s):  
Carotid Body ◽  
Normobaric Hypoxia ◽  
Sodium Potassium ◽  
Water Excretion ◽  
Excretory Function ◽  
Arterial Blood ◽  
Peripheral Arterial ◽  
Renal Responses ◽  
Arterial Po2 ◽  
Sodium And Potassium

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.

scholarly journals Evaluations about the physico-chemical stability of docetaxel and irinotecan pre-diluted and diluted solutions: pharmaco-economic perspectives

2013 ◽  
Vol 3 (1) ◽  
pp. 6 ◽  
Author(s):  
Mariarita Laforgia ◽  
Anna Elisa Quatrale ◽  
Nicola A. Colabufo ◽  
Amalia Azzariti ◽  
Angelo Paradiso ◽  
...  
Keyword(s):  
Chemical Stability ◽  
Mobile Phase ◽  
Ammonium Acetate ◽  
Physical Stability ◽  
Experimental Conditions ◽  
Phase Gradient ◽  
Methanol Mixture ◽  
Physico Chemical ◽  
Starting Point ◽  
Economic Perspectives

Several clinically used anticancer drugs are well-known as far as their pharmacologic properties are concerned, but scarcely ever the interest towards their physico-chemical characteristics in solution led to practical acknowledgement in their management. Thanks to the Units for Centralized Anticancer Drug Handling, the importance to evaluate the concentration of saturation (physical stability) or the possible transformations undergone by a drug in solution (chemical stability) has become the starting point for avoiding useless wasting drugs and economic resources. By HPLC experiments we have demonstrated that the solutions of two drugs, docetaxel and irinotecan, are particularly stable at different concentrations and times of analyses in our experimental conditions. The best mobile phase for docetaxel was water/methanol/acetonitrile in 42/32/26 volumetric ratio: for halving concentrations (0.72-0.36-0.18-0.09 mg/mL) in NaCl 0.9%, the highest value gave a six-day and the three lower concentrations a fourteen-day stability, when storage occurred at room temperature and light protected. Elution of irinotecan was possible through an analysis in mobile phase gradient: at t0 a 20% ammonium acetate 10 mM and 80% methanol mixture, and after 5 min, a 80% ammonium acetate 10 mM and 20% methanol mixture. The physico-chemical stability was showed for five days, for any concentration of analysis when storage occurred at 2-8°C and light protected.

scholarly journals Mechanism of the process of decomposition of apatitis with phosphoric acid

2019 ◽  
Vol 81 (1) ◽  
pp. 294-297
Author(s):  
R. F. Sabirov ◽  
A. F. Makhotkin ◽  
Yu. N. Sakharov ◽  
I. A. Makhotkin ◽  
I. Yu. Sakharov
Keyword(s):  
Phosphoric Acid ◽  
Ph Value ◽  
Batch Reactor ◽  
Experimental Studies ◽  
Hydrogen Ions ◽  
Experimental Conditions ◽  
Monocalcium Phosphate ◽  
Ph Values ◽  
Whole Process ◽  
Proportional Increase

Experimental studies of the kinetics and mechanism of the process, decomposition of apatite by phosphoric acid, in the Apatite-H3PO4-H2O system without the addition of sulfuric acid have been performed. The study of the decomposition process of Kovdorsky apatite with certain particle sizes was carried out in a batch reactor with a volume of 1 dm3 with stirring of the reaction mixture, and an initial concentration of phosphoric acid of 17% by weight, at a temperature of 78–82 °C. Observation of the process was carried out by determining the concentration of phosphoric acid and the concentration of monocalcium phosphate. The acidity of the reaction mixture was determined by the pH meter readings (pH-105 MA with a glass combined-ESC-10603 electrode). It was shown that during the whole process a constant smooth increase in the pH value of the reaction mixture to pH 6 occurs. Comparison of the pH values of the reaction mixture during the actual at the time of determining the concentration of phosphoric acid and pH of phosphoric acid of the corresponding concentration in the aqueous solution shows that the pH value of the reaction mixture is significantly affected by the presence of monocalcium phosphate gel. During the process, during the first thirty minutes, the concentration of phosphoric acid decreases from 17 to 10% by weight, the corresponding quantitative formation of monocalcium phosphate gel and a proportional increase in the pH of the reaction mixture. Then, as the concentration of phosphoric acid decreases, the process slows down and does not proceed to the end under the experimental conditions. The dependence of the concentration of hydrogen ions in the reaction mixture on the time of the process of decomposition of apatite in phosphoric acid, which is presented in logarithmic coordinates, shows that the mechanism of formation of hydrogen ions during the whole process does not change. Thus, it is shown that the process of decomposition of apatite by phosphoric acid in the Apatite-H3PO4-H2O system proceeds with the formation of an intermediate product - monocalcium phosphate gel. When this occurs, a corresponding significant change in the pH values of the reaction mixture occurs. During the whole process there is a constant decrease in the concentration of phosphoric acid.

scholarly journals ADSORPTION OF PHOSPHATE IONS ON RED SLUDGE

2017 ◽  
Vol 60 (8) ◽  
pp. 80
Author(s):  
Svetlana M. Kramer ◽  
Mariya V. Terekhova ◽  
Inna V. Artamonova
Keyword(s):  
Hydrochloric Acid ◽  
Experimental Studies ◽  
Aluminum Production ◽  
Quantitative Composition ◽  
Experimental Conditions ◽  
Initial Concentration ◽  
Phosphate Ions ◽  
Frumkin’S Isotherm ◽  
Ph Range ◽  
Red Sludge

In work the possibility of red sludge (waste of aluminum production by Bayer's method) to adsorb phosphate ions from water solutions at various concentration of ions and in the pH range from 3 to 10 is studied. Relevance of use of red sludge for receiving on its basis of sorbents is reasoned. For identification of the studied object the qualitative and quantitative composition of red sludge was established by the method of the X-ray phase analysis. The technique of red slage activation by hydrochloric acid, and also an adsorption technique of phosphate ions on the red sludge surface is described. Experimental studies of adsorption of phosphate ions on the surface of the red slage activated by hydrochloric acid depending on рН and concentration of initial solution were conducted. The dependence of adsorption phosphate ions on the red slage activated by НСl on рН and on the initial concentration of phosphate ions in solution is presented. These dependences of a relative fraction of distribution of various ions of phosphoric acid on рН are given in work. The form of ion phosphate having the greatest adsorptive activity on the red slage activated by hydrochloric acid in experimental conditions is revealed. Experimental data on dependence of adsorption of phosphate ions on their initial concentration in solution are described by Frumkin's isotherm. The constant of the adsorptive balance, limit adsorption, the parameter of intermolecular interaction of the adsorbed particles are calculated. Optimum conditions for adsorption of phosphate ions on red slage are established.Forcitation:Kramer S.M., Terekhova M.V., Artamonova I.V. Adsorption of phosphate ions on red sludge. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2017. V. 60. N 8. P. 80-83.

Sign in / Sign up

Export Citation Format

Share Document