Role of the Kidneys in Resistant Hypertension

Resistant hypertension is a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) in a patient who adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic. The kidneys play a critical role in long-term regulation of blood pressure. Blunted pressure natriuresis, with resultant increase in extracellular fluid volume, is an important cause of resistant hypertension. Activation of the renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity and increased sodium reabsorption are important renal mechanisms. Successful treatment requires identification and reversal of lifestyle factors or drugs contributing to treatment resistance, diagnosis and appropriate treatment of secondary causes of hypertension, use of effective multidrug regimens and optimization of diuretic therapy. Since inappropriate renal salt retention underlies most cases of drug-resistant hypertension, the therapeutic focus should be on improving salt depleting therapy by assessing and, if necessary, reducing dietary salt intake, optimizing diuretic therapy, and adding a mineralocorticoid antagonist if there are no contraindications.

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THE ROLE OF HIGH DIETARY SALT INTAKE IN DEVELOPMENT OF RESISTANT HYPERTENSION

Journal of Hypertension ◽

10.1097/01.hjh.0000539108.88656.fa ◽

2018 ◽

Vol 36 (Supplement 1) ◽

pp. e53

Author(s):

G. Khamidullaeva ◽

L. Khafisova ◽

A. Nagay ◽

D. Kurbanova ◽

N. Srojidinova

Keyword(s):

Resistant Hypertension ◽

Salt Intake ◽

Dietary Salt ◽

Dietary Salt Intake

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Lithium clearance in man: Effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide

Clinical Science ◽

10.1042/cs0730645 ◽

1987 ◽

Vol 73 (6) ◽

pp. 645-651 ◽

Cited By ~ 41

Author(s):

J. C. Atherton ◽

R. Green ◽

S. Hughes ◽

V. McFall ◽

J. A. Sharples ◽

...

Keyword(s):

Volume Expansion ◽

Salt Intake ◽

Extracellular Fluid ◽

Fluid Volume ◽

High Salt ◽

Extracellular Fluid Volume ◽

Lithium Clearance ◽

Dietary Salt ◽

Salt Diet ◽

Dietary Salt Intake

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3–4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water re-absorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.

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Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2

AJP Renal Physiology ◽

10.1152/ajprenal.00259.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. F1139-F1148 ◽

Cited By ~ 28

Author(s):

Ina Maria Schieβl ◽

Agnes Rosenauer ◽

Veronika Kattler ◽

Will W. Minuth ◽

Mona Oppermann ◽

...

Keyword(s):

Angiotensin Ii ◽

Salt Intake ◽

Sucrose Solution ◽

Salt Content ◽

Sodium Reabsorption ◽

Thick Ascending Limb ◽

Differential Splicing ◽

Dietary Salt ◽

Dietary Salt Intake ◽

Low Salt

Both sodium reabsorption in the thick ascending limb of the loop of Henle (TAL) and macula densa salt sensing crucially depend on the function of the Na/K/2Cl cotransporter NKCC2. The NKCC2 gene gives rise to at least three different full-length NKCC2 isoforms derived from differential splicing. In the present study, we addressed the influence of dietary salt intake on the differential splicing of NKCC2. Mice were subjected to diets with low-salt, standard salt, and high-salt content for 7 days, and NKCC2 isoform mRNA abundance was determined. With decreasing salt intake, we found a reduced abundance of the low-affinity isoform NKCC2A and an increase in the high-affinity isoform NKCC2B in the renal cortex and the outer stripe of the outer medulla. This shift from NKCC2A to NKCC2B during a low-salt diet could be mimicked by furosemide in vivo and in cultured kidney slices. Furthermore, the changes in NKCC2 isoform abundance during a salt-restricted diet were partly mediated by the actions of angiotensin II on AT1 receptors, as determined using chronic angiotensin II infusion. In contrast to changes in oral salt intake, water restriction (48 h) and water loading (8% sucrose solution) increased and suppressed the expression of all NKCC2 isoforms, without changing the distribution pattern of the single isoforms. In summary, the differential splicing of NKCC2 pre-mRNA is modulated by dietary salt intake, which may be mediated by changes in intracellular ion composition. Differential splicing of NKCC2 appears to contribute to the adaptive capacity of the kidney to cope with changes in reabsorptive needs.

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Arterial baroreceptor denervation impairs long-term regulation of arterial pressure during dietary salt loading

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.5.h1558 ◽

1998 ◽

Vol 275 (5) ◽

pp. H1558-H1566 ◽

Cited By ~ 31

Author(s):

John W. Osborn ◽

Barbara J. Hornfeldt

Keyword(s):

Arterial Pressure ◽

Salt Intake ◽

Critical Role ◽

Dietary Salt ◽

Dark Cycle ◽

Salt Loading ◽

Dietary Salt Intake ◽

The Third ◽

Arterial Baroreceptors

Experiments were performed to examine the contribution of arterial baroreceptors to long-term regulation of mean arterial pressure (MAP) during changes in dietary salt intake. Normotensive Sprague-Dawley rats were subjected to either sinoaortic denervation (SAD; n= 8) or Sham surgery ( n = 6) and instrumented 1 wk later with radiotelemetry transmitters for continuous minute-to-minute monitoring of MAP and heart rate (HR) over the 8-wk protocol. Rats consumed three levels of dietary NaCl: 0.4% NaCl ( week 1), 4.0% NaCl ( weeks 2–4), and 8.0% NaCl ( weeks 5–7). Rats returned to a 0.4% NaCl diet during the eighth week of the experiment. During week 1 (0.4% NaCl), there were no differences between Sham and SAD groups for 24-h averages of MAP or HR. However, by the third week of 4.0% NaCl, 24-h MAP was elevated significantly from baseline in SAD (10 ± 2 mmHg) but not Sham (1 ± 1 mmHg) rats. By the end of the third week of 8.0% NaCl diet, 24-h MAP was elevated 15 ± 2 mmHg above control in SAD rats compared with a 4 ± 1 mmHg increase in Sham rats ( P < 0.05). Hourly analysis of the final 72 h of each level of dietary salt revealed a marked effect of dietary NaCl on MAP in SAD rats, particularly during the dark cycle. MAP increased ∼20 and 30 mmHg in SAD rats over the 12-h dark cycle for 4.0 and 8.0% NaCl diets, respectively. In contrast, increased dietary NaCl had no effect on MAP during any phase of the light or dark period in Sham rats. These data support the hypothesis that arterial baroreceptors play a critical role in long-term regulation of MAP under conditions of altered dietary salt intake. Finally, hourly analysis of MAP revealed that the majority of the hypertensive response to increased NaCl occurs during the dark cycle in SAD rats. Hence, previous investigations may have underestimated the magnitude of the hypertensive response to increased dietary NaCl in animals with baroreceptor dysfunction.

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Abstract P332: Dietary Salt Intake and Blood Pressure Control in Hypertensive Individuals Under Antihypertensive Treatment During 7 Years

Hypertension ◽

10.1161/hyp.70.suppl_1.p332 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Kazuto Ohno ◽

Hiroyuki Takase ◽

Masashi Machii ◽

Daishi Nonaka ◽

Tomonori Sugiura ◽

...

Keyword(s):

Blood Pressure ◽

Antihypertensive Treatment ◽

Salt Intake ◽

Antihypertensive Drugs ◽

Dietary Salt ◽

Antihypertensive Medications ◽

Salt Restriction ◽

Hypertensive Patients ◽

Dietary Salt Intake ◽

Excess Salt Intake

Purpose: Excess salt intake is one of the most important causes of hypertension. Salt restriction is a key strategy in the management of hypertension and, thus, should be instructed for hypertensive patients under medical treatment. We investigated recent changes in dietary salt intake and blood pressure (BP) levels in hypertensive patients. Methods: Total of 12422 hypertensive subjects (male 71.0% [8814 of 12422], 64.6±9.2 year-old) under medical treatment who visited our hospital for a physical checkup from 2010 to 2016 were enrolled. They were divided into 3 groups according to the number of antihypertensive drugs prescribed (1, 2 and ≥3 drugs). Cross-sectional analyses were performed using data in each year and changes during the 7 years were investigated. Individual salt intake was estimated using a spot urine by a previously reported method. Results: BP levels and the accomplishment rate of the target BP (<140/90mmHg) were improved in each group during the 7 years without significant difference among the groups (Overall 2010 to 2016; BP 132.7±13.6/80.0±8.9 to 128.8±13.7/76.3±9.6 mmHg and accomplishment ratio 65.6 [968 of 1475] to 76.4% [1433 of 1875]). However, individual salt intake was gradually increased in all groups (2010 to 2016 in 1, 2, and ≥3 drugs; 11.7±3.7 to 12.2±4.0, 11.9±3.7 to 12.7±3.9, and 12.2±3.9 to 12.9±4.1 g/day, respectively) and the accomplishment rate of salt restriction (<6g/day) was significantly reduced in subjects with increased number of antihypertensive drugs (3.5 [225 of 6435], 2.8 [125 of 4564], and 2.3% [33 of 1423] in groups with 1, 2, and ≥3 drugs, respectively). The accomplishment rate of the target BP was significantly higher in patients who achieved salt restriction than in those who did not achieve salt restriction in all groups (Over all; 80.2 [307 of 383] vs. 73.3% [8829 of 12039]). Conclusions: The control of BP in individuals with antihypertensive medications was improved in the last 7 years. However, salt restriction has not been successfully achieved especially in hypertensive patients with multiple antihypertensive medications. Excess salt intake may induce resistance to antihypertensive treatment and, thus, increases the number of antihypertensive drugs for BP control.

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Faculty Opinions recommendation of Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717955767.793460736 ◽

2012 ◽

Author(s):

Hans Oberleithner

Keyword(s):

Blood Pressure ◽

Cardiovascular Diseases ◽

Salt Intake ◽

Dietary Salt ◽

Dietary Salt Intake

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The Effects of Different Kinds of Nutrition and Functional Foods on Multiple Sclerosis

Current Nutrition & Food Science ◽

10.2174/1573401316666200129115858 ◽

2020 ◽

Vol 16 (5) ◽

pp. 632-637

Author(s):

Masih Falahatian

Keyword(s):

Multiple Sclerosis ◽

Functional Foods ◽

Fruits And Vegetables ◽

Salt Intake ◽

Vegetable Intake ◽

Dietary Salt ◽

Negative Effects ◽

Dietary Salt Intake ◽

Neuroinflammatory Disease ◽

The Central Nervous System

It is an assumption that different kinds of nutrition, diet, and functional foods might have different positive or negative effects on multiple sclerosis (MS), a neuroinflammatory disease of the central nervous system (CNS). This brief paper involved a study on various kinds of nutrition including salt, fat, dairy, fruit, and vegetables. At the end of this study, appropriate diets were evaluated for MS patients. Based on previous studies both on animal models and on MS patients, excessive dietary salt intake and animal fat had worsening effects on MS patients but fruit and vegetable intake helped the remission of MS and decreased the risk of developing it. There were, of course, conflicting results in different studies over the role of some nutrition in MS and future studies on larger numbers of cases were required to collect reliable results. As a result, at the end of this study and based on literature, it is suggested that a diet should be programmed by nutritionists containing fewer salt, fat, and dairy intake and more fruits and vegetables for MS patients in order to better management of the disease.

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