Increased Renal Sensitivity to Aldosterone in the Potassium-Loaded Rat

1976 ◽  
Vol 51 (s3) ◽  
pp. 315s-317s
Author(s):  
W. R. Adam ◽  
J. W. Funder

1. The renal response to aldosterone (urinary sodium and potassium excretion) was determined in adrenalectomized rats previously fed either a high potassium diet or a control diet. High K+ rats showed an enhanced response to aldosterone at all doses tested. 2. This enhanced response to aldosterone required the presence of the adrenal glands during the induction period, could be suppressed by a high sodium intake, but could not be induced by a low sodium diet. 3. No difference between high K+ and control rats could be detected in renal mineralocorticoid receptors, assessed by both in vivo and in vitro binding of tritiated aldosterone. 4. The method of the induction, and the mechanism of the enhanced response, remain to be defined.

1989 ◽  
Vol 77 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Minoru Kawamura ◽  
Yuhei Kawano ◽  
Kaoru Yoshida ◽  
Masahito Imanishi ◽  
Satoshi Akabane ◽  
...  

1. Angiotensin (ANG) levels were measured in the cerebrospinal fluid of 15 patients with essential hypertension on a high sodium diet for 1 week and on a low sodium diet for a further week. ANGs were determined using a system of extraction by Sep-Pak cartridges followed by h.p.l.c. combined with radioimmunoassay. 2. Sodium depletion resulted in increases of ANG II in the cerebrospinal fluid from 1.16 ± 0.38 (sem) to 1.83 ± 0.43 fmol/ml (P < 0.01) and of ANG III from 0.65 ± 0.11 to 0.86 ± 0.15 fmol/ml (P < 0.01). 3. The ANG II level in the cerebrospinal fluid was found to be unchanged and recovery of added ANG II was approximately 90%, even after incubation for 3 h, on both diets. Thus, it is unlikely that ANG II is produced or degraded in the cerebrospinal fluid in vitro. 4. There was no significant correlation between the cerebrospinal fluid and the plasma ANG II concentration on the low sodium diet. 5. These results suggest that the cerebrospinal fluid ANG II level increases with sodium depletion, and that the effect of the level of ANG II on the activity of the angiotensin-forming system in the central nervous system may be assessed by determination of ANG II in the cerebrospinal fluid in patients with essential hypertension.


1983 ◽  
Vol 98 (2) ◽  
pp. 221-226 ◽  
Author(s):  
J. Alaghband-Zadeh ◽  
S. Fenton ◽  
K. Hancock ◽  
J. Millettt ◽  
H. E. de Wardener

Acetone extracts from a variety of rat tissues were tested for their ability to stimulate renal glucose-6-phosphate dehydrogenase (G6PD) activity at 2 min in an in-vitro cytochemical assay which is a marker of the sodium potassium-dependent adenosine triphosphatase (Na+-K+-ATPase) inhibiting activity. Extracts of the hypothalamus were the only ones found to be active in this system. Acetone extract of hypothalamus also inhibited renal Na+-K+-ATPase activity in vitro. The G6PD-stimulating activity from one hypothalamus was about 10000 to 100 000 times greater than that of 1 ml plasma. The G6PD-stimulating activity of hypothalamic extracts from rats which had been on a high sodium intake for 4 weeks were approximately 150 times more active than those obtained from rats which had been on a low sodium diet. The G6PD-stimulating activity of the corresponding plasma was sixfold more active. These findings suggest that a circulating sodium transport inhibitor(s) may be secreted from the hypothalamus.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Valerie K Sullivan ◽  
Lawrence J Appel ◽  
Jesse C Seegmiller ◽  
Casey M Rebholz

Background: The blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well-established. The effects on other biomarkers related to vascular health are of interest and may assist in explaining cardiovascular benefits of the DASH diet. Objective: We hypothesized that a low-sodium DASH diet improves biomarkers of inflammation [i.e. reduces C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)]. Methods: We conducted a post hoc analysis of the DASH-Sodium trial using stored frozen serum samples. This controlled feeding study randomized 412 adults to consume either a DASH diet or control diet representative of a typical American diet. Within each arm, participants received three sodium levels (low, intermediate, high) in random sequence, each for 30 days. To maximize contrast, samples collected at the end of the low-sodium DASH (n=198) and high-sodium control (n=194) diets were compared. Between-diet differences in biomarker concentrations were assessed by t-test or Wilcoxon rank sum test for normally distributed and skewed variables, respectively. Results: CRP concentrations did not differ between groups ( P =0.19), but suPAR was higher after the low-sodium DASH diet than the high-sodium control (median, IQR: 2473, 2127-2887 pg/mL vs. 2281, 1929-2679 pg/mL; P =0.003). FGF23 was also higher after the DASH diet (35.9, 26.9-44.8 pg/mL vs. 30.2, 23.5-37.5 pg/mL; P< 0.001). Serum phosphorus was higher after the DASH diet (mean±SEM: 3.5±0.04 mg/dL) versus the control (3.4±0.04 mg/dL; P =0.02). Conclusions: Contrary to our hypothesis, biomarkers of inflammation and mineral metabolism were increased or unchanged by a low-sodium DASH diet compared to a high-sodium control diet. Potential reasons (e.g. short duration of the trial, sodium-specific effects, bioavailable phosphorus-rich dairy intake) require further investigation.


BMJ ◽  
2019 ◽  
pp. l772 ◽  
Author(s):  
Martin O’Donnell ◽  
Andrew Mente ◽  
Sumathy Rangarajan ◽  
Matthew J McQueen ◽  
Neil O’Leary ◽  
...  

AbstractObjectiveTo evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.DesignInternational prospective cohort study.Setting18 high, middle, and low income countries, sampled from urban and rural communities.Participants103 570 people who provided morning fasting urine samples.Main outcome measuresAssociation of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).ResultsMean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).ConclusionsThese findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.


1977 ◽  
Vol 75 (2) ◽  
pp. 187-195 ◽  
Author(s):  
D. I. FATTAH ◽  
B. J. WHITEHOUSE ◽  
G. P. VINSON

Rat adrenal capsules incubated with [3H]18-hydroxydeoxycorticosterone (18-OH-DOC) and [3H]18-hydroxycorticosterone gave appreciable yields of aldosterone from both precursors, similar in size to those obtained from labelled corticosterone, deoxycorticosterone and progesterone under the same conditions. After feeding rats for 14 days on a flour diet deficient in sodium, aldosterone production from endogenous precursors in vitro was increased twofold compared with that by adrenal glands from animals receiving the flour diet with 1% sodium chloride added (control diet). When adrenal capsules from animals on the low-sodium flour diet were incubated with high specific activity [3H]18-OH-DOC (sp. act. 40 Ci/mmol), the yield of [3H]aldosterone was increased two- to threefold compared with that produced by capsules from animals on the control diet. When capsules were incubated with low specific activity [3H] 18-OH-DOC and [14C]corticosterone (sp. act. 52 mCi/mmol) only the yield of [14C]aldosterone was increased. Yields of labelled 18-hydroxycorticosterone from all precursors tested were increased three- to fourfold in animals receiving the low-sodium diet relative to the controls. The results show that 18-OH-DOC can be an effective precursor for aldosterone formation by rat adrenal capsules, and that production of aldosterone and 18-hydroxycorticosterone from this precursor can be stimulated by a low-sodium diet. This suggests the existence of an alternative pathway for aldosterone biosynthesis involving 18-OH-DOC as an intermediate.


2013 ◽  
Vol 304 (3) ◽  
pp. R260-R266 ◽  
Author(s):  
Julie O'Neill ◽  
Alan Corbett ◽  
Edward J. Johns

Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1–7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1–7). Renal interstitial infusion of angiotensin (1–7) in anesthetized rats fed a normal salt intake had minimal effects on glomerular filtration rate but caused dose-related increases in urine flow and absolute and fractional sodium excretions ranging from 150 to 200%. In rats maintained for 2 wk on a low-sodium diet angiotensin (1–7) increased glomerular filtration rate by some 45%, but the diuretic and natriuretic responses were enhanced compared with those in rats on a normal sodium intake. By contrast, renal interstitial infusion of angiotensin (1–7) in rats maintained on a high-sodium intake had no effect on glomerular filtration rate, whereas the diuresis and natriuresis was markedly attenuated compared with those in rats fed either a normal or low-sodium diet. Plasma renin and angiotensin (1–7) were highest in the rats on the low-sodium diet and depressed in the rats on a high-sodium diet. These findings demonstrate that the renal hemodynamic and excretory responses to locally administered angiotensin (1–7) is dependent on the level of sodium intake and indirectly on the degree of activation of the renin-angiotensin system. The exact way in which angiotensin (1–7) exerts its effects may be dependent on the prevailing levels of angiotensin II and its receptor expression.


2020 ◽  
Vol 158 (4) ◽  
pp. 339-348
Author(s):  
Tamer M. M. Hassan ◽  
Omar A. Ahmed-Farid ◽  
Fathy A. I. Abdel-Fattah

AbstractPomegranate peels (PP) and mango leaves (ML) were analysed for nutrients and tannin contents. In an in vitro test, ten diets were prepared; six contained 2, 4 and 6% of PP or ML, three diets supplemented with mixed levels of PP and ML (1 + 1%, 2 + 2% and 3 + 3%) and control diet free of them. Gas was measured after 3, 6, 12, 24, 48 and 72 h of incubation. Methane and rumen parameters were estimated. In an in vivo experiment, 40 Ossimi lambs were divided into four groups; the first was control, other groups (T1, T2 and T3) fed diets containing 6% PP, 6% ML or mix levels (3% PP + 3%ML), respectively, for 2 months. Results showed that PP and ML were rich in tannins. In the in vitro test, a maximum reduction in gas, methane and NH3-N was in 6% PP, 6% ML and mixed levels (3% PP + 3% ML). In the in vivo experiment, there were no differences in growth and digestibility of DM and nutrients between treatment groups. Only a lowered DM intake and protein digestibility in lambs fed 6% PP. Gas and methane emission was decreased significantly in lambs fed 6% PP, compared to other groups. TVFAs and NH3-N were decreased for treatment groups. Also, all treatments did not show any pathological changes in liver function or on oxidative stress markers. In conclusion, PP and ML can be used in sheep diets at inclusion levels of 6% and mixture without detrimental effects on general health of Ossimi lambs.


1968 ◽  
Vol 58 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Jürg Müller

ABSTRACT Three groups of rats received respectively the following drinking fluids for two weeks: sucrose 5%; NaCl 0.154 m + sucrose; KCl 0.154 m+ sucrose. Aldosterone biosynthesis by quartered adrenal glands of these animals was studied under various in vitro conditions. Adrenals from rats drinking sucrose alone produced significantly more aldosterone under all conditions of incubation than adrenals from rats drinking NaCl, which produced more corticosterone and deoxycorticosterone. Tissue from animals drinking NaCl converted less unlabelled progesterone, 11β-hydroxyprogesterone, deoxycorticosterone and corticosterone to aldosterone and incorporated less tritiated pregnenolone, progesterone, deoxycorticosterone and corticosterone into aldosterone. Adrenals from rats drinking KCl produced less aldosterone than adrenals from rats drinking sucrose under basal conditions but not under stimulation by ACTH or potassium ions. In both groups, the production of corticosterone and of deoxycorticosterone was the same under various test conditions. These results indicate that a high sodium intake inactivates one or both enzymes essential for the conversion of corticosterone to aldosterone, whereas a high potassium intake has no significant effect on these later steps of aldosterone biosynthesis.


1987 ◽  
Vol 108 (1) ◽  
pp. 237-243 ◽  
Author(s):  
H. Martens ◽  
O. W. Kubel ◽  
G. Gäbel ◽  
H. Honig

SummaryThree sheep, equipped with cannulae in the dorsal rumen sac, abomasum and ileum, were fed a low sodium diet of artifically dried young grass. Mean daily intake of sodium was 310 mg. The sheep were given daily supplements of 0 or 2·3 g sodium by an intraruminal infusion.The concentration of K in mixed saliva and ruminal fluid from the sheep not given sodium supplements increased and the concentration of Na decreased markedly. The changes in the ion concentrations were associated with an increase of the transmural potential difference across the ruminal epithelium.The altered ion concentrations of Na and K in the ruminal fluid and the increased potential difference were accompanied by a decrease in Mg absorption from the forestomachs. The apparent availability of Mg from the gastrointestinal tract decreased from 34·5 (sodium supplementation) to 22·3 (low sodium intake).It is suggested that a daily intake of Na of 310 mg did not cover the sodium requirement of these sheep and that a low sodium intake influences the absorption of Mg in a similar manner as it has been observed with a high K intake.The results are discussed in context of grass tetany in ruminants. It is suggested that an inadequate intake of sodium is an overlooked factor of the pathogenesis of this disease.


2021 ◽  
Author(s):  
Rosa D Wouda ◽  
Femke Waanders ◽  
Dick de Zeeuw ◽  
Gerjan Navis ◽  
Liffert Vogt ◽  
...  

Abstract Background Angiotensin receptor blockers (ARBs) lower blood pressure (BP) and proteinuria and reduce renal disease progression in many—but not all—patients. Reduction of dietary sodium intake improves these effects of ARBs. Dietary potassium intake affects BP and proteinuria. We set out to address the effect of potassium intake on BP and proteinuria response to losartan in non-diabetic proteinuric chronic kidney disease (CKD) patients. Methods We performed a post-hoc analysis of a placebo-controlled interventional cross-over study in 33 non-diabetic proteinuric patients (baseline mean arterial pressure and proteinuria: 105 mmHg and 3.8 g/d, respectively). Patients were treated for 6 weeks with placebo, losartan, and losartan/hydrochlorothiazide, combined with a habitual (∼200 mmol/d) and low-sodium diet (&lt;100 mmol/d), in randomized order. To analyze the effects of potassium intake, we categorized patients based on median split of 24 h urinary potassium excretion, reflecting potassium intake. Results Mean potassium intake was stable during all 6 treatment periods. Losartan and losartan/hydrochlorothiazide lowered BP and proteinuria in all treatment groups. Patients with high potassium intake showed no difference in the BP effects compared to patients with low potassium intake. The antiproteinuric response to losartan monotherapy and losartan combined with hydrochlorothiazide during the habitual sodium diet was significantly diminished in patients with high potassium intake (20% vs. 41%, p = 0.011 and 48% vs 64%, p = 0.036). These differences in antiproteinuric response abolished when shifting to the low sodium diet. Conclusions In proteinuric CKD patients, the proteinuria, but not BP-lowering response to losartan during a habitual high sodium diet was hampered during high potassium intake. Differences disappeared after sodium status change by low-sodium diet.


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