Urinary Excretion of 20-Hete, Natriuresis and Salt-Sensitivity of Blood Pressure in Essential Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 716-716
Author(s):  
Cheryl L Laffer ◽  
Michal Laniado-Schwartzman ◽  
Mong-Heng Wang ◽  
Alberto Nasjletti ◽  
Fernando Elijovich
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Urinary Excretion ◽  
Salt Sensitivity ◽  
Nacl Transport ◽  
Salt Loading ◽  
Pm 10 ◽  
Salt Sensitive Hypertension ◽  
The Relationship ◽  
Na Depletion

P127 20-hydroxyeicosatetraenoic acid (20-HETE) inhibits NaCl transport in the loop of Henle. A deficit in its synthesis or action has been implicated in experimental salt-sensitive hypertension. We examined the relationship between urinary excretion of Na (UNaV) and 20-HETE in 26 essential hypertensive patients classified as salt-sensitive (SS=13) or resistant (SR=13) by an in-patient protocol of 24 hr salt-loading (HI: 160 mEq Na diet+2L saline iv) followed by 24-hr sodium deprivation (LO: 10 mEq Na diet+furosemide 120 mg in first 12 hrs). SS was defined as a fall in ambulatory systolic BP (SBP, noon to 10 pm)≥10 mmHg from HI to LO. The Table shows data in HI and in the second 12 hr period of LO, i.e., after Na depletion was achieved by furosemide. SS and SR did not differ in any of these data. 20-HETE did not correlate with race, age, or GFR. During HI, it showed a negative correlation with BMI (r=-0.44, p<0.03) and a positive one with BP (r=+0.42, p<0.04). Also, 20-HETE correlated with UNaV in all patients (r=+0.45, p<0.02), but this was due to a strong correlation in SR (r=+0.62, p<0.03), absent in SS. In LO, no correlations were observed between any of these measurements. Our data demonstrate that 20-HETE excretion varies with the state of salt-balance in human hypertension and diminishes with increasing obesity. Although excretion of 20-HETE is not different between SS and SR, there is a major difference in the relationship between excretion of this eicosanoid and natriuresis between these groups. Our data suggest that salt-sensitivity of blood pressure in human essential hypertension may result from impairment in a natriuretic mechanism dependent on 20-HETE.

Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways

2015 ◽  
Vol 308 (5) ◽  
pp. F377-F387 ◽  
Author(s):  
Mitsuhiro Nishimoto ◽  
Toshiro Fujita
Keyword(s):  
Blood Pressure ◽  
Salt Sensitivity ◽  
Diagnostic Tools ◽  
Electrolyte Balance ◽  
Renal Tubules ◽  
Adrenergic Stimulation ◽  
Salt Loading ◽  
Histone Deacetylase 8 ◽  
Collecting Ducts ◽  
Salt Sensitive Hypertension

Although salt is a major environmental factor in the development of hypertension, the degree of salt sensitivity varies widely among individuals. The mechanisms responsible for this variation remain to be elucidated. Recent studies have revealed the involvement of two important signaling pathways in renal tubules that play key roles in electrolyte balance and the maintenance of normal blood pressure: the β2-adrenergic stimulant-glucocorticoid receptor (GR)-with-no-lysine kinase (WNK)4-Na+-Cl− cotransporter pathway, which is active in distal convoluted tubule (DCT)1, and the Ras-related C3 botulinum toxin substrate (Rac)1-mineralocorticoid receptor (MR) pathway, which is active in DCT2, connecting tubules, and collecting ducts. β2-Adrenergic stimulation due to increased renal sympathetic activity in obesity- and salt-induced hypertension suppresses histone deacetylase 8 activity via cAMP/PKA signaling, increasing the accessibility of GRs to the negative GR response element in the WNK4 promoter. This results in the suppression of WNK4 transcription followed by the activation of Na+-Cl− cotransporters in the DCT and elevated Na+ retention and blood pressure upon salt loading. Rac1 activates MRs, even in the absence of ligand binding, with this activity increased in the presence of ligand. In salt-sensitive animals, Rac1 activation due to salt loading activates MRs in DCT2, connecting tubules, and collecting ducts. Thus, GRs and MRs are independently involved in two pathways responsible for renal Na+ handling and salt-sensitive hypertension. These findings suggest novel therapeutic targets and may lead to the development of diagnostic tools to determine salt sensitivity in hypertensive patients.

scholarly journals Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

2008 ◽  
Vol 36 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Yong Liu ◽  
Ravinder J. Singh ◽  
Kristie Usa ◽  
Brian C. Netzel ◽  
Mingyu Liang
Keyword(s):  
Blood Pressure ◽  
Urinary Excretion ◽  
Molecular Mechanisms ◽  
Renal Medulla ◽  
Hydroxysteroid Dehydrogenase ◽  
Induced Hypertension ◽  
Intensive Investigation ◽  
Salt Sensitive Hypertension ◽  
Interfering Rna

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11β-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11β-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

scholarly journals Reduction in Monocyte Isolevuglandins Associated with High Interstitial Sodium Mirrors Salt‐Sensitivity of Blood Pressure in Patients with Essential Hypertension

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Melis Sahinoz ◽  
Fernando Elijovich ◽  
Cheryl Laffer ◽  
Ashley Pitzer ◽  
Talat Ikizler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Salt Sensitivity

scholarly journals Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats

2016 ◽  
Vol 310 (2) ◽  
pp. R115-R124 ◽  
Author(s):  
Kathryn R. Walsh ◽  
Jill T. Kuwabara ◽  
Joon W. Shim ◽  
Richard D. Wainford
Keyword(s):  
Blood Pressure ◽  
Sodium Chloride ◽  
Salt Sensitivity ◽  
Dietary Sodium ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sodium Chloride Cotransporter ◽  
Sprague Dawley Rats ◽  
Salt Sensitive Hypertension ◽  
The Impact

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.

Time-course of changes in intracellular cations and blood pressure with salt loading in patients with essential hypertension

1991 ◽  
Vol 9 ◽  
pp. S304 ◽  
Author(s):  
Mari Kainouchi ◽  
Hideo Matsuura ◽  
Tetsuji Shingu ◽  
Ichiro Inoue ◽  
Takafumi Ishida ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Time Course ◽  
Salt Loading

Endogenous Erythropoietin and Salt Sensitivity of Blood Pressure in Patients With Essential Hypertension

1993 ◽  
Vol 6 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Shojiro Naomi ◽  
Teruhisa Umeda ◽  
Taisuke Iwaoka ◽  
Joji Yamauchi ◽  
Yasufumi Ideguchi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Salt Sensitivity ◽  
Endogenous Erythropoietin

The Relationship of Blood Pressure to Hospitalization, Dietary Sodium and Serum Renin in Essential Hypertension

Angiology ◽  
1970 ◽  
Vol 21 (2) ◽  
pp. 75-82 ◽  
Author(s):  
Daniel K. Bloomfield ◽  
Anne B. Gould ◽  
JOSE L. Cangiano ◽  
Victor Vertes
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Human Serum ◽  
Direct Relationship ◽  
Dietary Sodium ◽  
Relationship Of ◽  
The Relationship ◽  
Methods Of Measurement ◽  
Sensitive Method

A direct relationship between the level of renin in the blood and the height of the blood pressure in humans has not been definitely established. Hitherto, the development of methods of measurement of renin has been fraught with great technical difficulties. Recently, Gould et al. developed a sensitive method for the assay of renin in human serum. The use of this method has enabled us to undertake a study of the relationship of the level of circulating renin in the blood to the height of the blood pressure under various conditions in patients with essential hypertension. The main purpose of this study was to determine whether there is a relationship between the level of circulating renin in the blood and the fall of blood pressure which occurs as a result of hospitalization and reduction of dietary sodium.

Renin-angiotensin-aldosterone system of the normothermic marmot

1977 ◽  
Vol 233 (1) ◽  
pp. R37-R43
Author(s):  
P. R. Kastner ◽  
M. L. Zatzman ◽  
F. E. South ◽  
J. A. Johnson
Keyword(s):  
Blood Pressure ◽  
Mammalian Species ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Salt Loading ◽  
Renin Angiotensin ◽  
Adrenal Steroid ◽  
Adrenal Secretion ◽  
Na Depletion ◽  
Secretion Rates

Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.

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