Deletion of Kir5.1 abolishes the effect of high-Na+-intake on Kir4.1 and Na-Cl-cotransporter.

2021 ◽  
Author(s):  
Xin-Peng Duan ◽  
Peng Wu ◽  
Dan-Dan Zhang ◽  
Zhong-Xiuzi Gao ◽  
Yu Xiao ◽  
...  
Keyword(s):  
Excretion Rate ◽  
Sodium Intake ◽  
Reversal Potential ◽  
Inhibitory Effect ◽  
Distal Nephron ◽  
High Sodium ◽  
Expression Activity ◽  
Epithelial Sodium Channel Enac ◽  
Stimulation Of

High-sodium-intake (HS) inhibited epithelial-sodium-channel (ENaC) in the aldosterone-sensitive-distal-nephron (ASDN) and Na+-Cl--cotransporter (NCC) by suppressing basolateral Kir4.1/Kir5.1 in the distal-convoluted-tubule (DCT) thereby increasing renal Na+ excretion but not affecting K+ excretion. The aim of the present study is to explore whether the deletion of Kir5.1 compromises the inhibitory effect of HS on NCC expression/activity and renal K+-excretion. Patch-clamp experiments demonstrated that HS failed to inhibit DCT-basolateral K+ channels and did not depolarize K+-currents (IK) reversal-potential of the DCT in Kir5.1 knockout (Kir5.1 KO) mice. Moreover, deletion of Kir5.1 not only increased the expression of Kir4.1, phosphor-NCC (pNCC) and total NCC (tNCC) but also abolished the inhibitory effect of HS on the expression of Kir4.1, pNCC and tNCC, and thiazide-induced natriuresis. Also, LS-induced stimulation of NCC expression/activity and the basolateral K+ channels in the DCT was absent in Kir5.1 KO mice. The deletion of Kir5.1 decreased ENaC currents in DCT2 and HS further inhibited ENaC activity in Kir5.1 KO mice. Finally, the measurement of basal renal K+ excretion rate with modified renal clearance method demonstrated that long-term HS inhibited renal K+ excretion rate and steadily increased plasma K+ levels in Kir5.1 KO mice but not in WT mice. We conclude that Kir5.1 plays an important role in mediating the effect of HS intake on the basolateral K+ channels in the DCT and NCC activity/expression. Kir5.1 is involved in maintaining renal ability of K+ excretion during HS intake.

Deletion of renal Nedd4-2 abolishes the effect of high sodium intake (HS) on Kir4.1, ENaC and NCC, and causes hypokalemia during HS.

2021 ◽  
Author(s):  
Dan-Dan Zhang ◽  
Xin-Peng Duan ◽  
Yu Xiao ◽  
Peng Wu ◽  
Zhong-Xiuzi Gao ◽  
...  
Keyword(s):  
Sodium Intake ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
High Sodium ◽  
Low Salt ◽  
Salt Sensitive Hypertension ◽  
Deficient Mice

Nedd4-2 regulates the expression of Kir4.1, thiazide-sensitive Na-Cl-cotransporter (NCC) and epithelial Na+ channel (ENaC) in aldosterone-sensitive-distal-nephron (ASDN) and Nedd4-2-deletion causes salt-sensitive hypertension. We now examine whether Nedd4-2-deletion compromises the effect of high salt (HS) on Kir4.1, NCC, ENaC and renal K+ excretion. Immunoblotting showed that HS decreased the expression of Kir4.1, Ca2+-activated-big-conductance K+-channel subunit-a (BKa), ENaCb, ENaCg, total NCC (tNCC) and phosphor-NCC (pNCC at Thr53) in Nedd4lflox/flox mice while these effects were absent in kidney-specific Nedd4-2-knockout (Ks-Nedd4-2 KO) mice. Patch-clamp experiments showed that neither HS nor low salt (LS) had effect on Kir4.1/Kir5.1 currents of the distal convoluted tubule (DCT) in Nedd4-2-deficient mice while we confirmed that HS inhibited and LS increased Kir4.1/Kir5.1 activity in Nedd4lflox/flox mice. Nedd4-2-deletion increased ENaC currents in the ASDN and this increase was more robust in the cortical-collecting-duct (CCD) than in the DCT. Also, HS-induced inhibition of ENaC currents in the ASDN was absent in Nedd4-2-deficient mice. Renal clearance experiments showed that HS intake for two-weeks increased the basal level of renal K+ excretion and caused hypokalemia in Ks-Nedd4-2-KO mice but not in Nedd4lflox/flox mice. In contrast, plasma Na+ concentrations were similar in Nedd4lflox/flox and Ks-Nedd4-2 KO mice on HS. We conclude that Nedd4-2 plays an important role in mediating inhibitory effect of HS on the Kir4.1, ENaC and NCC; and is essential for maintaining a normal renal K+ excretion and plasma K+ ranges during long-term HS.

Atrial natriuretic factor and blood pressure control: role of sodium and aldosterone

1990 ◽  
Vol 259 (5) ◽  
pp. R973-R980 ◽  
Author(s):  
C. A. Gaillard ◽  
H. L. Mizelle ◽  
J. P. Montani ◽  
M. W. Brands ◽  
D. A. Hildebrandt ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Sodium Intake ◽  
Control Period ◽  
Hypotensive Effect ◽  
Long Term Effects ◽  
High Sodium ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

This study examined the long-term actions of atrial natriuretic factor (ANF), at physiological levels, on renal function and mean arterial pressure (MAP) and the importance of Na intake and the renin-angiotensin-aldosterone system in modulating those effects. After a control period, ANF was infused intravenously at a rate of 10 ng.kg-1.min-1 for 7 days, followed by 7 days of 20 ng.kg-1.min-1 and 7 days of recovery. After 7 days of ANF at 10 ng.kg-1.min-1, MAP decreased from 87 +/- 3 to 80 +/- 2 mmHg in normal dogs on low sodium intake (LS, 7 meq Na/day) and from 89 +/- 2 to 79 +/- 2 mmHg in adrenalectomized dogs (ADX, 7 meq Na/day) given constant mineralocorticoid replacement. In both groups, no significant change in glomerular filtration rate (GFR) was observed, although sodium excretion increased transiently. ANF failed to cause significant changes in MAP, GFR, or sodium excretion in normal dogs on high sodium intake (HS, 269 meq Na/day). In LS and HS no long-term effects of ANF on plasma renin activity (PRA) and aldosterone were observed. In ADX, as expected, no change in aldosterone was observed. Thus, in normal and adrenalectomized dogs on LS, chronic ANF infusion caused sustained reductions in MAP. HS markedly attenuated the hypotensive effect of ANF. Our data suggest that the long-term effect of ANF is salt sensitive but that decreases in PRA and aldosterone are not essential for the long-term hypotensive effect of ANF.

Role of nitric oxide in the arterial pressure and renal adaptations to long-term changes in sodium intake

1997 ◽  
Vol 272 (4) ◽  
pp. R1162-R1169 ◽  
Author(s):  
R. D. Manning ◽  
L. Hu ◽  
J. F. Reckelhoff
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Sodium Intake ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Control Group ◽  
High Sodium ◽  
Sodium Sensitivity ◽  
High Sodium Intake

The goals of this study were to determine whether long-term nitric oxide (NO) synthesis inhibition in dogs results in an increase in the sodium sensitivity of arterial pressure and whether changes in plasma renin activity or the plasma concentrations of arginine vasopressin (AVP) and aldosterone play an important role in this hypertension. Studies were conducted in a control group and groups that received NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 or 25 microg x kg(-1) x min(-1). Each group was challenged with normal, low, and high sodium intake for periods of 5 days each. Urinary nitrate + nitrite excretion (UNOx) more than doubled in the control group during high sodium intake. In both L-NAME groups, UNOx decreased significantly, there was a hypertensive shift in the relation between urinary sodium excretion and arterial pressure, and urinary sodium excretion remained normal even in the high-sodium intake period. L-NAME infusion did not change the sodium sensitivity of arterial pressure or plasma renin activity, plasma aldosterone, and plasma AVP. In conclusion, the data suggest that, in dogs, increases in NO synthesis are not necessary to excrete a chronic sodium load, and decreases in NO do not increase the sodium sensitivity of arterial pressure.

Chronic activation of brain areas by high-sodium diet in Dahl salt-sensitive rats

1998 ◽  
Vol 274 (6) ◽  
pp. H2046-H2052 ◽  
Author(s):  
Adam S. Budzikowski ◽  
Faranak Vahid-Ansari ◽  
Frans H. H. Leenen
Keyword(s):  
Sodium Intake ◽  
Brain Areas ◽  
Hypothalamic Area ◽  
High Sodium ◽  
Sodium Diet ◽  
Transient Activation ◽  
Nucleus Of Solitary Tract ◽  
Central Gray ◽  
High Sodium Diet

To map changes in neuronal activity in the brains of Dahl salt-sensitive (Dahl S) vs. salt-resistant (Dahl R) rats by high-sodium diet, we used immunohistochemical detection of Fra-like proteins as a marker for long-term neuronal activation. Compared with Dahl R rats during regular sodium intake, Dahl S rats showed modestly higher expression of Fra-like immunoreactivity (Fra-LI) in the supraoptic nucleus, anterior hypothalamic area (AHA), central gray, and nucleus of solitary tract (NTS) at 5, 6, and 9 wk of age but clearly elevated Fra-LI in the magnocellular part of the paraventricular nucleus (PVN) at 6 wk of age (but not at 5 and 9 wk). In the median preoptic nucleus (MnPO) Fra-LI was lower at 9 wk of age and no differences were observed in the parvocellular PVN and subfornical organ in Dahl S vs. Dahl R rats on regular sodium intake. Compared with Dahl S rats on a regular-sodium diet, Dahl S rats on a high-sodium diet from 4 to 9 wk of age had significantly increased blood pressure and experienced transient activation of magnocellular PVN and MnPO and virtually no changes in the activity of the parvocellular PVN, AHA, and NTS. In contrast, Dahl R rats showed marked activation in the magnocellular PVN after 1 and 2 wk on a high-sodium diet compared with Dahl R rats on a regular-sodium diet. The present study demonstrates that Dahl S rats show differential activation of brain areas participating in regulation of osmotic and cardiovascular homeostasis during development of sodium-sensitive hypertension.

scholarly journals Effects of long term exposure to aluminium stress on the accumulation and distribution of K+, Na+, Ca2+, Mg2+, Fe2+ and Clin rice and chickpea plants

2018 ◽  
Vol 27 (1) ◽  
pp. 37-48
Author(s):  
Rifat Samad ◽  
Parveen Rashid ◽  
JL Karmoker
Keyword(s):  
Inhibitory Effect ◽  
Mineral Nutrients ◽  
Sand Culture ◽  
Nutrients Uptake ◽  
Maximum Inhibition ◽  
Al Treatment ◽  
Different Parts ◽  
Stimulation Of

Sand culture experiments were undertaken to examine the effect of increasing aluminium levels (50-150 μM) on the mineral nutrients uptake (K+, Na+, Ca2+, Mg2+, Fe2+ and Cl-). Increasing concentrations of Al inhibited the uptake of K+, Ca2+, Mg2+ and Fe2+ but enhanced that of Na+ and Cl- in the root and shoot of rice, and the root, stem and leaves of chickpea. 150 μM Al caused a maximum inhibition of K+ accumulation in the root and shoot of rice ranging from 25.5 to 49.0% and 33 to 55.5%, respectively, from 7 to 28 day of treatment. In the root, stem and leaves of chickpea, 150 μM Al inhibited K+ content by 23.9 to 84.0%, 13.2 to 54.4% and 25.3 to 61.2%, respectively, from 7 to 28 day of application. On the contrary, a dramatic 2.7 to 3.1-folds and 70.8% to 2.3-folds stimulation of Na+ accumulation was recorded in the root of rice and chickpea, respectively, following 100 μM Al treatment from 7 to 28 day of treatment. Different concentrations of aluminium led to a stimulation of Cl- accumulation in different parts of rice and chickpea plants. In rice and chickpea plants, the inhibitory effect of aluminium stress on the accumulation of Ca2+, Mg2+ and Fe2+ was enhanced with the increase in Al concentration from 50 to 150 μM. Dhaka Univ. J. Biol. Sci. 27(1): 37-48, 2018 (January)

The Development of Patterned Activity by implanted Ganglia and their Peripheral Connexions in Periplaneta Americana

1969 ◽  
Vol 50 (1) ◽  
pp. 255-273
Author(s):  
D. M. GUTHRIE ◽  
J. R. BANKS
Keyword(s):  
Periplaneta Americana ◽  
Functional Relationship ◽  
Low Frequency ◽  
Inhibitory Effect ◽  
Sense Organs ◽  
Steady Level ◽  
The Central Nervous System ◽  
Stimulation Of

1. The isolation of a thoracic ganglion from the rest of the central nervous system results in a loss of differentiation of the motor output, although repetitive rhythms may appear during the later stages of isolation. Total isolation of the ganglion in vitro results in a further reduction of motor activity to low-frequency, steady-level discharges in a few fibres of some nerves only. 2. Two or three months after implantation a steady low-frequency discharge can be recorded from many of the branches of the implant ganglion, and these may have functional contacts with adjacent muscles. There is little evidence of afferent connexions. 3. Four to seven months after implantation the efferent connexions of the implanted ganglion often show a highly differentiated pattern of spontaneous electrical activity, and the ganglion will respond in a remarkably delayed and progressive manner to the stimulation of adjacent sense organs. 4. The spontaneous rhythms of the long-term implant ganglion may be determined by a balance between central and peripheral input levels similar to those occurring during progressive isolation of the ganglion. 5. The functional relationship between the host and the donor ganglion appears to consist largely of an inhibitory effect exerted by the host ganglion on the donor or implant ganglion. A justification for this in adaptive terms can be found.

Dietary sodium induced cardiac hypertrophy

1992 ◽  
Vol 70 (4) ◽  
pp. 580-586 ◽  
Author(s):  
Eef Harmsen ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Adrenergic Receptors ◽  
Ventricular Hypertrophy ◽  
Sodium Intake ◽  
Left Ventricular ◽  
Dietary Sodium ◽  
Adrenergic Stimulation ◽  
High Sodium ◽  
High Sodium Intake ◽  
Stimulation Of

In humans, high sodium intake not only increases the blood pressure, and thus can cause left ventricular hypertrophy (LVH), but also appears to increase LVH independent of this increase in blood pressure. In both normo- and hyper-tensive rats the hypertrophic effect of increased dietary sodium intake on the heart has been clearly established. In normotensive rats, this effect is strain and age dependent, and seems independent of hemodynamic effects of high sodium intake. In both rats and humans, dietary sodium appears to increase wall thickness, resembling pressure overload rather than an increased left ventricular diameter as expected of volume overload. The mechanisms through which high dietary sodium induces hypertrophy are still unknown. It is possible that dietary sodium increases either adrenergic stimulation and (or) enhances sensitivity for adrenergic stimulation and that this hypertrophic response mainly acts via stimulation of α1-adrenergic receptors. Stimulation of the α1-adrenergic receptors will increase the inositol phosphate – diacyl glycerol pathway and enhance the Na+/H+ exchange. The activity of this exchanger might play an important role in the development of dietary sodium induced cardiac hypertrophy.Key words: heart, dietary sodium, left ventricular hypertrophy, hemodynamics, sympathetic activity.

"IN VIVO RADIOIMMUNOASSAY" OF ALDOSTERONE

1973 ◽  
Vol 74 (2) ◽  
pp. 307-315 ◽  
Author(s):  
P. Vecsei ◽  
K. H. Gless ◽  
M. Winter ◽  
M. Hanka-Postozky
Keyword(s):  
Plasma Concentration ◽  
Sodium Intake ◽  
Binding Capacity ◽  
The Body ◽  
Aldosterone Secretion ◽  
High Sodium ◽  
High Sodium Intake ◽  
The Relationship ◽  
Stimulation Of

ABSTRACT Aldosterone antibodies were raised in sheep immunized with a complex of D-aldosterone-21-hemisuccinate and bovine serum albumin. The intravenous injection of these antibodies into rats caused a delay in the disappearance rate of tritiated aldosterone from the blood. The degree of this effect depends on the body weight of the animals, on the amount of the antiserum given, and on the interval between the injection of antibodies and that of labelled aldosterone. After the injection of aldosterone antibodies and the tritiated hormone, the plasma concentration of labelled aldosterone was related to the rate of secretion of the hormone. When aldosterone secretion was low, subsequent to high sodium intake, or abolished after adrenalectomy, the plasma concentration of tritiated aldosterone was higher than in the control rats. Stimulation of aldosterone secretion by furosemide or ACTH, or administration of cold aldosterone resulted in a decrease in the plasma concentration of the labelled hormone. It is suggested that the relationship between the amount of free aldosterone in the "inner pool" and the plasma concentration of tritiated aldosterone is the consequence of a competition of labelled and unlabelled hormone for the binding capacity of the antibody.

Deep brain stimulation of the posterior limb of the internal capsule in the treatment of central poststroke neuropathic pain of the lower limb: case series with long-term follow-up and literature review

2020 ◽  
Vol 133 (3) ◽  
pp. 830-838 ◽  
Author(s):  
Andrea Franzini ◽  
Giuseppe Messina ◽  
Vincenzo Levi ◽  
Antonio D’Ammando ◽  
Roberto Cordella ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Lower Limb ◽  
Internal Capsule ◽  
Posterior Limb ◽  
Vas Score ◽  
The Mean ◽  
Deep Brain ◽  
Stimulation Of

OBJECTIVECentral poststroke neuropathic pain is a debilitating syndrome that is often resistant to medical therapies. Surgical measures include motor cortex stimulation and deep brain stimulation (DBS), which have been used to relieve pain. The aim of this study was to retrospectively assess the safety and long-term efficacy of DBS of the posterior limb of the internal capsule for relieving central poststroke neuropathic pain and associated spasticity affecting the lower limb.METHODSClinical and surgical data were retrospectively collected and analyzed in all patients who had undergone DBS of the posterior limb of the internal capsule to address central poststroke neuropathic pain refractory to conservative measures. In addition, long-term pain intensity and level of satisfaction gained from stimulation were assessed. Pain was evaluated using the visual analog scale (VAS). Information on gait improvement was obtained from medical records, neurological examination, and interview.RESULTSFour patients have undergone the procedure since 2001. No mortality or morbidity related to the surgery was recorded. In three patients, stimulation of the posterior limb of the internal capsule resulted in long-term pain relief; in a fourth patient, the procedure failed to produce any long-lasting positive effect. Two patients obtained a reduction in spasticity and improved motor capability. Before surgery, the mean VAS score was 9 (range 8–10). In the immediate postoperative period and within 1 week after the DBS system had been turned on, the mean VAS score was significantly lower at a mean of 3 (range 0–6). After a mean follow-up of 5.88 years, the mean VAS score was still reduced at 5.5 (range 3–8). The mean percentage of long-term pain reduction was 38.13%.CONCLUSIONSThis series suggests that stimulation of the posterior limb of the internal capsule is safe and effective in treating patients with chronic neuropathic pain affecting the lower limb. The procedure may be a more targeted treatment method than motor cortex stimulation or other neuromodulation techniques in the subset of patients whose pain and spasticity are referred to the lower limbs.

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