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

2014 ◽  
Author(s):  
Daniel Beard
Keyword(s):  
Mathematical Model ◽  
Kidney Function ◽  
Hormonal Regulation ◽  
Water Excretion ◽  
Pressure Natriuresis

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.

Role of the renal medulla in volume and arterial pressure regulation

1997 ◽  
Vol 273 (1) ◽  
pp. R1-R15 ◽  
Author(s):  
A. W. Cowley
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Fluid Pressure ◽  
Regulatory System ◽  
Renal Medulla ◽  
Water Excretion ◽  
Vasa Recta ◽  
Pressure Natriuresis ◽  
Total Renal Blood Flow

The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.

scholarly journals 117 THE INOSINIC BRANCH POINT AND ITS HORMONAL REGULATION. EVALUATION THROUGH A MATHEMATICAL MODEL

1988 ◽  
Vol 24 (1) ◽  
pp. 130-130
Author(s):  
Maria Pizzichini ◽  
Anna Di Stefano ◽  
Germano Resconi ◽  
Enrico Marinello
Keyword(s):  
Mathematical Model ◽  
Branch Point ◽  
Hormonal Regulation

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.

Body fluids and electrolytes after prolonged cardiopulmonary bypass

1964 ◽  
Vol 19 (4) ◽  
pp. 566-570 ◽  
Author(s):  
Dorothy Brinsfield ◽  
M. A. Hopf ◽  
S. E. Mayer ◽  
P. M. Galletti
Keyword(s):  
Hormonal Regulation ◽  
Extracellular Fluid ◽  
Cellular Level ◽  
Assisted Circulation ◽  
Electrolyte Balance ◽  
Acid Base Balance ◽  
Water Excretion ◽  
Electrolyte Retention ◽  
Base Balance ◽  
Total Body

Fluid and electrolyte balance was studied in 21 dogs after partial heart-lung bypass of 10 hr duration. Water retention was demonstrated by an increase in body weight and total body water, primarily due to an increase in extracellular fluid. Electrolyte retention was suggested by an increase in total extracellular sodium, potassium, and chloride. Urinary output was relatively normal but a progressive drop in urinary specific gravity was observed during bypass. Blood pH remained essentially unchanged. However, an increase in plasma lactate and a decrease in plasma bicarbonate suggested some degree of hypoxia and metabolic acidosis at the cellular level. Altered hormonal regulation of sodium and water excretion, hemolysis secondary to blood trauma, and the exchange of intracellular potassium for extracellular hydrogen ions were considered possible explanation for the fluid and electrolyte changes observed. assisted circulation; heart-lung bypass; acid-base balance; fluid balance; extracorporeal circulation; electrolyte changes with partial bypass; membrane oxygenator; disc oxygenator; bubble oxygenator Submitted on June 20, 1963

Renal autoregulation and pressure natriuresis during ANF-induced diuresis

1987 ◽  
Vol 253 (3) ◽  
pp. F424-F431 ◽  
Author(s):  
R. V. Paul ◽  
K. A. Kirk ◽  
L. G. Navar
Keyword(s):  
Arterial Pressure ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Similar Response ◽  
Water Excretion ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
Pressure Natriuresis ◽  
Atrial Natriuretic

We examined the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) in the anesthetized dog during selective renal arterial infusion of two different synthetic atrial natriuretic factor (ANF) analogues. Rat atriopeptin II (5 X 10(-8) M in renal arterial blood) caused increases in sodium and water excretion but left RBF and GFR unchanged. A similar response was seen with rat 8-33 atrial natriuretic peptide (ANP) (10(-9) M), but a twofold higher dose of this peptide produced a transient increase in RBF and a sustained 16% increase in GFR. The normal pattern of RBF autoregulation in response to decreases in renal perfusion pressure was not altered by either peptide. GFR was also efficiently autoregulated during ANF infusion; however, there was a threefold increase in the slope of the relationship between sodium excretion and arterial pressure (pressure natriuresis) during 8-33 ANP infusion (control 1.11 +/- 0.39, 8-33 ANP 4.00 +/- 0.86 mu eq/mmHg, P less than 0.01). We conclude that ANF-induced diuresis can be sustained without detectable changes in either the autoregulation-responsive or autoregulation-independent components of renal vascular resistance. Factors other than GFR, which are highly responsive to renal perfusion pressure, are important in modulating the natriuresis caused by ANF. The augmentation of pressure natriuresis within the GFR autoregulatory range suggests an influence of ANF on the magnitude of arterial pressure-induced changes in tubular sodium reabsorption.

Blockade of pressure natriuresis induced by inhibition of renal synthesis of nitric oxide in dogs

1992 ◽  
Vol 262 (5) ◽  
pp. F718-F722 ◽  
Author(s):  
M. G. Salom ◽  
V. Lahera ◽  
F. Miranda-Guardiola ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Inhibitory Effect ◽  
Synthesis Inhibitor ◽  
Urine Sodium ◽  
Water Excretion ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis ◽  
Acute Changes

To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg-1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP.

scholarly journals Endothelin-1 inhibits sodium reabsorption by ETA and ETB receptors in the mouse cortical collecting duct

2013 ◽  
Vol 305 (4) ◽  
pp. F568-F573 ◽  
Author(s):  
I. Jeanette Lynch ◽  
Amanda K. Welch ◽  
Donald E. Kohan ◽  
Brian D. Cain ◽  
Charles S. Wingo
Keyword(s):  
Hormonal Regulation ◽  
Collecting Duct ◽  
Early Response ◽  
Sodium Reabsorption ◽  
Na Channel ◽  
Cortical Collecting Duct ◽  
Water Excretion ◽  
Endothelin 1 ◽  
Arterial Blood

The collecting duct (CD) is a major renal site for the hormonal regulation of Na homeostasis and is critical for systemic arterial blood pressure control. Our previous studies demonstrated that the endothelin-1 gene (edn1) is an early response gene to the action of aldosterone. Because aldosterone and endothelin-1 (ET-1) have opposing actions on Na reabsorption (JNa) in the kidney, we postulated that stimulation of ET-1 by aldosterone acts as a negative feedback mechanism, acting locally within the CD. Aldosterone is known to increase JNa in the CD, in part, by stimulating the epithelial Na channel (ENaC). In contrast, ET-1 increases Na and water excretion through its binding to receptors in the CD. To date, direct measurement of the quantitative effect of ET-1 on transepithelial JNa in the isolated in vitro microperfused mouse CD has not been determined. We observed that the CD exhibits substantial JNa in male and female mice that is regulated, in part, by a benzamil-sensitive pathway, presumably ENaC. ENaC-mediated JNa is greater in the cortical CD (CCD) than in the outer medullary CD (OMCD); however, benzamil-insensitive JNa is present in the CCD and not in the OMCD. In the presence of ET-1, ENaC-mediated JNa is significantly inhibited. Blockade of either ETA or ETB receptor restored JNa to control rates; however, only ETA receptor blockade restored a benzamil-sensitive component of JNa. We conclude 1) Na reabsorption is mediated by ENaC in the CCD and OMCD and also by an ENaC-independent mechanism in the CCD; and 2) ET-1 inhibits JNa in the CCD through both ETA and ETB receptor-mediated pathways.

scholarly journals MATHEMATICAL MODELING AND CONTROL OF HIV INFECTION DYNAMICS TAKING INTO ACCOUNT HORMONAL REGULATION

2019 ◽  
Vol 23 (1) ◽  
pp. 79-103 ◽  
Author(s):  
A. A. Savinkova ◽  
R. S. Savinkov ◽  
B. A. Bakhmetyev ◽  
G. A. Bocharov
Keyword(s):  
Quality Of Life ◽  
Mathematical Model ◽  
Side Effects ◽  
Hiv Infection ◽  
Hormonal Regulation ◽  
Optimization Methods ◽  
Cost Of Drugs ◽  
The Cost ◽  
The Mathematical Model

Aims: The problem of effective treatment of HIV-infected patients is an important task of clinical virology and immunology due to the high cost of drugs, the presence of side effects and the need for strict adherence to the schedule of drug intake for patients. Therefore, the urgent task is to develop new approaches to optimize the use of antiretroviral therapy to reduce the cost of treatment and to improve the quality of life for patients. The tasks are addressed to test the hypothesis that the system of therapeutic interruptions in the treatment of HIV infection can give better results (both the duration and comfort of the patient’s life, and the need for fewer drugs) compared with regular medication in standard doses. Methods: In this work, an extended version of the mathematical model of the immune response in HIV infection (proposed in Hadjiandreou et al., 2009) was constructed to take into account the hormonal regulation of the immune response and the impact of antiretroviral drugs on the course of the disease, the calibration of the parameters of the resulting model to match the actual trends of the disease and the search for an optimal treatment strategy. The model is formulated as a system of ordinary differential equations. The therapy optimization is modeled following the structured treatment interruptionapproach using the methods of simulated annealing and the simplex method. The mathematical model and optimization methods are implemented in C ++. Results: It has been shown that in treating HIV-infected patients, it is possible to significantly (up to 3 times) reduce the total amount of required medications simultaneously with an increase in the duration of the period with a high quality of life (due to reducing the intensity of side effects) during antiretroviral therapy. Conclusion: The use of mathematical models and optimization methods opens up the possibility for the implementation of personalized approaches to the treatment of HIV infection, taking into account the side effects, the hormonal status of patients and the cost of drugs.

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