Abstract P147: Attenuation Of Diuretic And Natriuretic Responses To Acute Saline Volume Expansion In Mice Pre-treated With Tumor Necrosis Factor-alpha (TNFα) Inhibitor, Etanercept.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Dewan S Majid ◽  
Alexander Castillo
Keyword(s):  
Intravenous Infusion ◽  
Volume Expansion ◽  
Salt Intake ◽  
Isotonic Saline ◽  
Physiological Role ◽  
Baseline Period ◽  
Sodium Reabsorption ◽  
High Salt Intake ◽  
Intravenous Saline ◽  
Tnfα Inhibitor

High salt intake induces an immune response that activates the mononuclear phagocyte system (MPS) cells to produce TNFα. We have previously demonstrated that intravenous infusion of TNFα in mice induces diuresis and natriuresis by inhibiting renal tubular sodium reabsorption. We hypothesize that the intravenous saline infusion can also induce the production of TNFα from MPS cells and such increase in TNFα influences saline induced natriuresis in the kidney. To examine this hypothesis, we measured the changes in TNFα levels in plasma and in urinary excretion rate (U TNFα V) during intravenous infusion of isotonic saline (0.9% NaCl), first at euvolemic condition (3 μL/min for 60 min; Baseline period) and then at an enhanced infusion rate (12 μL/min for 90 min; Volume expansion period) in anesthetized mice (n=5). Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances respectively. TNFα concentration in plasma and urine samples were determined using ELISA kit (Ebioscience, Woburn, MA). TNFα level in plasma collected during baseline period was undetectable, however, TNFα was increased to 3.7±1.3 pg/mL during volume expansion (VE) period. Baseline U TNFα V level was 0.01±0.002 pg/min/g (kidney wt), which was increased to 0.11±0.03 pg/min/g (P<0.05) during VE period. VE increased urine flow (V, 5.4±0.5 to 22.0±5.1 μL/min/g; P<0.05) and sodium excretion (U Na V; 0.54±0.19 to 4.84 ±1.16 μmol/min/g; P<0.05) without significant changes in RBF (7.1±1.0 to 6.0±1.8 mL/min/g) and GFR (1.18±0.11 to 0.94±0.28 mL/min/g). Interestingly, the diuretic and natriuretic responses to VE were markedly attenuated in mice (n=5) pretreated with a TNFα inhibitor, etanercept (ETN; 0.5 mg/kg intraperitoneally once daily for 3 days prior to the experiment day). VE induced changes in ETN treated mice are as follows: V, 5.9±0.65 to 7.9 ±1.6 μL/min/g; U Na V, 0.43±0.6 to 1.1±0.28 μmol/min/g; RBF, 5.4±0.4 to 6.6±0.9 mL/min/g and GFR, 0.87±0.09 to 0.98±0.13 mL/min/g. These findings demonstrate for the first time that an intravenous saline volume infusion resulted an increase in TNFα level in plasma and in urine. These results strongly suggest a physiological role for TNFα in regulating renal excretory function during saline volume expansion.

scholarly journals Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs

2009 ◽  
Vol 296 (2) ◽  
pp. R265-R271 ◽  
Author(s):  
Michael W. Brands ◽  
Tracy D. Bell ◽  
Nancy A. Rodriquez ◽  
Praveen Polavarapu ◽  
Dmitriy Panteleyev
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Salt Intake ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Glucose Infusion ◽  
Sodium Reabsorption ◽  
Tubular Sodium Reabsorption ◽  
High Salt Intake ◽  
Sustained Increase

This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg·kg−1·min−1 iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging ∼20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs.

scholarly journals A Mouse Model for Liddle's Syndrome

1999 ◽  
Vol 10 (12) ◽  
pp. 2527-2533 ◽  
Author(s):  
SYLVAIN PRADERVAND ◽  
QING WANG ◽  
MICHEL BURNIER ◽  
FRIEDRICH BEERMANN ◽  
JEAN DANIEL HORISBERGER ◽  
...  
Keyword(s):  
Mouse Model ◽  
Salt Intake ◽  
Sodium Reabsorption ◽  
Dietary Salt ◽  
Human Form ◽  
Dominant Form ◽  
Liddle’S Syndrome ◽  
High Salt Intake ◽  
Liddle's Syndrome ◽  
Salt Sensitive Hypertension

Abstract. Liddle's syndrome (or pseudoaldosteronism) is an autosomal dominant form of salt-sensitive hypertension, due to abnormal sodium transport by the renal tubule. To study the pathophysiology of salt sensitivity, a mouse model for Liddle's syndrome has been generated by Cre/loxP-mediated recombination. Under normal salt diet, mice heterozygous (L/+) and homozygous (L/L) for Liddle mutation (L) develop normally during the first 3 mo of life. In these mice, BP is not different from wild type despite evidence for increased sodium reabsorption in distal colon and low plasma aldosterone, suggesting chronic hypervolemia. Under high salt intake, the Liddle mice develop high BP, metabolic alkalosis, and hypokalemia accompanied by cardiac and renal hypertrophy. This animal model reproduces to a large extent a human form of salt-sensitive hypertension and establishes a causal relationship between dietary salt, a gene expressed in kidney and hypertension.

Suppressive action of prolactin on renal response to volume expansion

1975 ◽  
Vol 229 (1) ◽  
pp. 81-85 ◽  
Author(s):  
MS Lucci ◽  
HH Bengele ◽  
S Solomon
Keyword(s):  
Volume Expansion ◽  
Isotonic Saline ◽  
Sodium Reabsorption ◽  
Physical Factors ◽  
Water Load ◽  
Renal Response ◽  
Water Handling ◽  
Male Wistar Rats ◽  
Diuretic Response ◽  
Ovine Prolactin

The effects of prolactin on rat renal sodium and water handling during volume expansion were studied using clearance techniques. Both control and experimental adult male Wistar rats were prehydrated with an oral water load of volume equal to 2.5% body weight (BW). At least 3 h later, a continuous intravenous infusion of ovine prolactin (NIH-P-S8), 7.1 mug/h per 100 g, was started in the experimental group. After a 1-h steady-state period, the rats were given an intravenous expansion infusion of either hypotonic saline (2.5% BW), isotonic saline (2.5% and 7.5% BW), or blood (2.5% BW). In all control hypotonic and isotonic saline-expanded animals, within 1 h the rats excreted a volume of urine equal to over 50% of the volume of saline infused. The diuretic and natriuretic responses to saline expansion of prolactin-treated rats were significantly smaller than controls. In contrast to the effects of prolactin on the renal response to saline infusions, it did not alter the natriuretic or diuretic response to blood infusion. Prolactin may be counteracting the effects of physical factors on the regulation of sodium reabsorption in the proximal tubule.

Interactions between subtotal nephrectomy and salt: effects on blood pressure and renal function in pregnant and nonpregnant ewes

2008 ◽  
Vol 294 (4) ◽  
pp. R1227-R1233 ◽  
Author(s):  
Karen J. Gibson ◽  
Amanda C. Boyce ◽  
Clare L. Thomson ◽  
Sarah Chinchen ◽  
Eugenie R. Lumbers
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Salt Intake ◽  
High Salt ◽  
Late Gestation ◽  
Plasma Creatinine ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
High Salt Intake ◽  
In Pregnancy

The effects of high salt intake on blood pressure and renal function were studied in nine subtotally nephrectomized pregnant ewes (STNxP) and seven intact pregnant ewes (IntP) in late gestation and in eight subtotally nephrectomized nonpregnant ewes (STNxNP) and seven intact nonpregnant ewes (IntNP). STNxP had higher mean arterial pressures ( P < 0.02) and plasma creatinine levels ( P < 0.001) than IntP. High salt (0.17 M NaCl as drinking water for 5 days) did not change blood pressure in either STNxP or IntP. STNxNP had higher mean arterial pressures ( P = 0.03) and plasma creatinine levels ( P < 0.001) than IntNP. In STNxNP, blood pressure increased with high salt intake and there was a positive relationship between diastolic pressure and sodium balance ( r = 0.497, P = 0.05). This relationship was not present in IntNP, STNxP, or IntP. Because high salt intake did not cause an increase in blood pressure in STNxP, it is concluded that they were protected by pregnancy from further rises in blood pressure. The observed increase in glomerular filtration rate ( P < 0.03) and depression of fractional proximal sodium reabsorption ( P = 0.003) that occurred in STNxP, but not in STNxNP, in response to high salt may have contributed to this protection. As well, the increased production of vasorelaxants in pregnancy may selectively protect against the occurrence of salt-sensitive hypertension in pregnancy.

Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP

1996 ◽  
Vol 271 (1) ◽  
pp. R109-R114 ◽  
Author(s):  
S. W. John ◽  
A. T. Veress ◽  
U. Honrath ◽  
C. K. Chong ◽  
L. Peng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Volume ◽  
Volume Expansion ◽  
Salt Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Blood Volume Expansion ◽  
High Salt Intake ◽  
Low Salt

Atrial natriuretic peptide (ANP)-gene knockout mice of three genotypes (+/+, +/-, and -/-) were maintained on a low-salt diet (0.008% NaCl). They were then fed either the same low-salt diet or a high-salt diet (8% NaCl) for 1 wk. No differences were found among genotypes in daily food and water intakes or in urinary volume and electrolyte excretions. Arterial blood pressures measured in anesthetized animals at the end of the dietary regimen were significantly and similarly increased in -/- compared with +/+ mice on each diet. Renal excretion of fluid and electrolytes was measured in anesthetized mice before and after acute blood volume expansion. No genotype differences were observed before volume expansion. After volume expansion the wild-type (+/+) mice had much greater saluretic responses than either the heterozygous (+/-) or the homozygous mutant (-/-) animals on the low-salt diet but not on the high-salt diet. We conclude that ANP lowers blood pressure in the absence of detected changes in renal function; ANP is not essential for normal salt balance, even on high-salt intake; and ANP is essential for the natriuretic response to acute blood volume expansion on a low-salt but not high-salt intake.

Influence of Volume Expansion on Renal Diluting Capacity in the Rat

1974 ◽  
Vol 46 (3) ◽  
pp. 331-345
Author(s):  
M. Martinez-Maldonado ◽  
G. Eknoyan ◽  
W. N. Suki
Keyword(s):  
Volume Expansion ◽  
Collecting Duct ◽  
Isotonic Saline ◽  
Extracellular Fluid ◽  
Free Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Sodium Reabsorption ◽  
Water Excretion ◽  
Hypotonic Saline

1. The functional capacity of Henle's loop was examined during hypotonic, isotonic and hypertonic extracellular fluid volume expansion. To eliminate a possible role of antidiuretic hormone (ADH) in the alteration of free water excretion, rats with congenital diabetes insipidus were used. The infusion of hypotonic saline resulted in a progressive rise in free water clearance (CH2O) throughout the range of urine flow (V) attained. Similar results were obtained in rats treated chronically with deoxycorticosterone acetate (DOCA). The infusion of isotonic saline (sodium chloride, 154 mmol/l) produced an initial rise in CH2O until V represented 10% of the filtered load, after which CH2O appeared to reach a plateau. The limitation of CH2O was more marked when hypertonic saline was infused. Medullary and papillary non-urea solute (NUS) concentration rose progressively with the increasing concentration of the saline solution infused. 2. The greater fractional sodium excretion (FENa) after acute isotonic and hypertonic volume expansion is probably the result of inhibition of sodium reabsorption in the collecting duct, although inhibition in the ascending limb cannot be entirely excluded. The depression of CH2O as a function of V seen during acute isotonic or hypertonic volume expansion can be attributed in part to enhanced water back-diffusion from the collecting duct consequent to the increasing medullary and papillary interstitial NUS concentration, even in the absence of ADH. 3. Chronic expansion of extracellular fluid volume by DOCA administration did not modify the response to hypotonic saline infusion.

Behaviour of Adrenomedullin during Acute and Chronic Salt Loading in Normotensive and Hypertensive Subjects

1996 ◽  
Vol 91 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Toshihiko Ishimitsu ◽  
Toshio Nishikimi ◽  
Hiroaki Matsuoka ◽  
Kenji Kangawa ◽  
Kazuo Kitamura ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Salt Intake ◽  
Isotonic Saline ◽  
Salt Loading ◽  
Salt Load ◽  
High Salt Intake ◽  
Normotensive Subjects ◽  
Atrial Natriuretic

1. Responses of adrenomedullin to acute and chronic salt loading were examined in normotensive and hypertensive subjects. 2. In the acute salt load study, isotonic saline (50 ml/kg for 1 h) was intravenously infused into nine normotensive subjects and 11 patients with essential hypertension. Plasma adrenomedullin was higher in hypertensive than in normotensive subjects but was unchanged by saline infusion in either the normotensive (before infusion, 2.4 ± 0.2 fmol/ml; after infusion, 2.4±0.1 fmol/ml) or hypertensive (before infusion, 3.0±0.1 fmol/ml; after infusion, 2.9 ± 0.2 fmol/ml) group, while renin was suppressed and atrial natriuretic peptide was markedly increased. Plasma endothelin was not affected either. 3. In the chronic salt load study, seven normotensive subjects and 23 patients with essential hypertension underwent two 7-day periods of 30 and 260 mmol/day sodium intake. Depending on the blood pressure change, 13 hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive. Salt-sensitive hypertensive subjects had suppressed plasma renin activity even during low salt intake. Plasma adrenomedullin or endothelin were not affected by the salt intake changes in any group; however, the high salt intake increased atrial natriuretic peptide in all groups. 4. These data indicate that the circulating level of adrenomedullin is not changed by either acute or chronic salt loading in normotensive subjects and patients with essential hypertension.

SALURETIC ACTION OF ALDOSTERONE IN THE PRESENCE OF INCREASED SALT INTAKE AND RESTORATION OF NORMAL ACTION BY PROLACTIN OR BY OXYTOCIN

1972 ◽  
Vol 55 (2) ◽  
pp. 369-376 ◽  
Author(s):  
P. G. BURSTYN ◽  
D. F. HORROBIN ◽  
M. S. MANKU
Keyword(s):  
Salt Intake ◽  
Isotonic Saline ◽  
High Salt ◽  
Sodium Potassium ◽  
Water Excretion ◽  
Intravenous Injections ◽  
Treatment Regimes ◽  
High Salt Intake ◽  
Collection Period ◽  
Pituitary Prolactin

SUMMARY The effects of aldosterone on sodium, potassium and water excretion during various treatment regimes were studied in six Merino ewes. Urine was collected from 12.00 to 14.00 h and from 14.00 to 16.00 h each day. Intravenous injections of either 1 ml isotonic saline or 500 μg aldosterone were given at 13.30 h and excretion during the second collection period compared with that in the first. When each animal was given a salt (NaCl) supplement of 80 mequiv./day by i.v. injection, aldosterone caused marked sodium retention with no effect on potassium. When salt supplements of 400 mequiv./day were given, aldosterone lost its sodium-retaining action in all animals and caused a marked saluresis with a small increase in potassium excretion in five sheep out of six. Injections of sheep pituitary prolactin or of oxytocin restored the sodium-retaining action of aldosterone in spite of a continued high salt intake. The animals gained very little weight when treated with 400 mequiv. salt alone but did gain significantly when treated with salt plus prolactin. The weight gain was rapidly lost when the prolactin and high salt intake were discontinued.

scholarly journals Epithelial Sodium Channel and Salt-Sensitive Hypertension

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 759-767
Author(s):  
Stephanie M. Mutchler ◽  
Annet Kirabo ◽  
Thomas R. Kleyman
Keyword(s):  
Blood Pressure ◽  
Sodium Channel ◽  
Salt Intake ◽  
Extracellular Fluid ◽  
Pressure Rise ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
High Salt Intake ◽  
Salt Sensitive Hypertension

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

Sign in / Sign up

Export Citation Format

Share Document