NO generation and action during changes in salt intake: roles of nNOS and macula densa

1998 ◽  
Vol 274 (6) ◽  
pp. R1588-R1593 ◽  
Author(s):  
Christopher S. Wilcox ◽  
Xiaolin Deng ◽  
William J. Welch
Keyword(s):  
Salt Intake ◽  
Selective Inhibitor ◽  
No Synthase ◽  
Macula Densa ◽  
Volume Replacement ◽  
Salt Loading ◽  
Salt Restriction ◽  
Low Salt ◽  
Renal Action ◽  
Renal Vascular

Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats ( n = 6–10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3(NOX) was increased during HS (LS: 9.0 ± 0.5 vs. HS: 15.7 ± 0.8 μmol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 ± 1.3 vs. HS: 9.4 ± 1.6 μmol/24 h; NS). During nonselective blockade of NOS with N G-nitro-l-arginine methyl ester (l-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 ± 17 vs. LS: +83 ± 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 ± 6 vs. LS: +34 ± 8%; NS) or F with volume replacement (HS: +79 ± 11 vs. LS: +62 ± 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.

scholarly journals Role of Renocortical Cyclooxygenase-2 for Renal Vascular Resistance and Macula Densa Control of Renin Secretion

2001 ◽  
Vol 12 (5) ◽  
pp. 867-874
Author(s):  
HAYO CASTROP ◽  
FRANK SCHWEDA ◽  
KARL SCHUMACHER ◽  
KONRAD WOLF ◽  
ARMIN KURTZ
Keyword(s):  
Vascular Resistance ◽  
Macula Densa ◽  
Renal Vascular Resistance ◽  
Renin Secretion ◽  
Expression Level ◽  
Flow Rates ◽  
Low Salt ◽  
Cox 2 ◽  
Renal Vascular

Abstract. This study aimed to assess the role of cyclooxygenase-2 (COX-2)-derived prostanoids for the macula densa control of renal afferent arteriolar resistance and for renin secretion. For this purpose, studied were the effects of blocking macula densa salt transport by the loop diuretic bumetanide (100 μM) on renal perfusate flow and on renin secretion in isolated perfused rats, in which renocortical COX-2 expression was prestimulated in vivo by treatment with the angiotensin-converting enzyme inhibitor ramipril, with low-salt diet, or with a combination of both. These maneuvers stimulated COX-2 expression in an order of ramipril + low salt ≫ low salt > ramipril > controls. Flow rates through isolated kidneys at a constant pressure of 100 mmHg were dependent on the pretreatment regimen, in the way that they went in parallel with COX-2 expression. The COX-2 inhibitor NS-398 (10 μM) lowered flow rates depending on the COX-2 expression level and was most pronounced therefore after pretreatment with low salt + ramipril. NS-398 did not change the increase of flow in response to bumetanide but attenuated the stimulation of renin secretion in response to bumetanide in a manner depending on the expression level of COX-2. These findings suggest that in states of increased renocortical expression of COX-2, overall renal vascular resistance and the macula densa control of renin secretion become dependent on COX-2—derived prostanoids.

Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. R410-R417 ◽  
Author(s):  
Atsushi Sakima ◽  
Hiroshi Teruya ◽  
Masanobu Yamazato ◽  
Rijiko Matayoshi ◽  
Hiromi Muratani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
High Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
Air Jet ◽  
Sd Rats ◽  
Low Salt ◽  
The Brain

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg ⋅ kg−1 ⋅ day−1of N G-monomethyl-l-arginine (l-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 ± 3 mmHg vs. 114 ± 3, 113 ± 1, and 108 ± 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats givenl-NMMA than in rats given aCSF (29 ± 4% vs. 19 ± 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats givenl-NMMA than in rats given aCSF irrespective of salt intake, although the difference was ∼7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.

Regulation of the energy sensor AMP-activated protein kinase in the kidney by dietary salt intake and osmolality

2005 ◽  
Vol 288 (3) ◽  
pp. F578-F586 ◽  
Author(s):  
Scott Fraser ◽  
Peter Mount ◽  
Rebecca Hill ◽  
Vicki Levidiotis ◽  
Frosa Katsis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Salt Intake ◽  
Macula Densa ◽  
High Salt ◽  
Thick Ascending Limb ◽  
Apical Surface ◽  
Western Blots ◽  
Α Subunit ◽  
Low Salt ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a key controller of cellular energy metabolism. We studied its expression and regulation by salt handling in the kidney. Immunoprecipitation and Western blots of protein lysates from whole rat kidney using subunit-specific antibodies showed that the α1-catalytic subunit is expressed in the kidney, associated with the β2- and either γ1- or γ2-subunits. Activated AMPK, detected by immunohistochemical staining for phospho-Thr172 AMPK (pThr172), was expressed on the apical surface of the cortical thick ascending limb of the loop of Henle, including the macula densa, and some parts of the distal convoluted tubule. Activated AMPK was also expressed on the basolateral surface of the cortical and medullary collecting ducts as well as some portions of the distal convoluted tubules. AMPK activity was increased by 25% in animals receiving a high-salt diet, and this was confirmed by Western blotting for pThr172. Low-salt diets were associated with reduced levels of the α-subunit of AMPK, which was highly phosphorylated on Thr172. Surprisingly, both low- and high-salt media transiently activated AMPK in the macula densa cell line MMDD1, an effect due to changes in osmolality, rather than Na+ or Cl− concentration. This study, therefore, demonstrates regulation of AMPK by both a high- and a low-salt intake in vivo and suggests a role for the kinase in the response to changes in osmolality within the kidney.

scholarly journals Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule

2008 ◽  
Vol 295 (1) ◽  
pp. F37-F41 ◽  
Author(s):  
Aaron Kulick ◽  
Carolina Panico ◽  
Pritmohinder Gill ◽  
William J. Welch
Keyword(s):  
Proximal Tubule ◽  
Salt Intake ◽  
Selective Inhibitor ◽  
Receptor Expression ◽  
Local Production ◽  
Low Salt ◽  
And Function ◽  
Rat Proximal Tubule

Adenosine mediates Na+ reabsorption in the proximal tubule (PT) and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the PT is regulated by salt intake and participates in the kidney adaptation to changes in salt intake. Absolute fluid reabsorption ( Jv) was measured by direct in vivo microperfusion and recollection in rats maintained on low (LS; 0.03% Na, wt/wt)-, normal (NS; 0.3% Na)-, and high-salt (HS; 3.0% Na) diets for 1 wk. The effect of microperfusion of BG9719 a highly selective inhibitor of A1-ARs or adenosine deaminase (AD), which metabolizes adenosine, was measured in each group. Jv was higher in PT from LS rats (LA: 2.8 ± 0.2 vs. NS: 2.1 ± 0.2 nl·min−1·mm−1, P < 0.001). Jv in HS rats was not different from NS. BG9719 reduced Jv in LS rats by 66 ± 6% (LS: 2.8 ± 0.2 vs LS+CVT: 1.3 ± 0.3 nl·min−1·mm−1, P < 0.001), which was greater than its effect in NS (45 ± 4%) or HS (41 ± 4%) rats. AD reduced Jv similarly, suggesting that A1-ARs are activated by local production of adenosine. Expression of A1-AR mRNA and protein was higher ( P < 0.01) in microdissected PTs in LS rats compared with NS and HS. We conclude that A1-ARs in the PT are increased by low salt intake and that A1-AR participates in the increased PT reabsorption of solute and fluid in response to low salt intake.

Influence of salt on response to nitrendipine by Dahl rat kidney

1987 ◽  
Vol 252 (3) ◽  
pp. F487-F490
Author(s):  
T. H. Steele ◽  
L. Challoner-Hue
Keyword(s):  
Filtration Rate ◽  
Channel Blocker ◽  
Rat Kidney ◽  
High Salt ◽  
Similar Response ◽  
Salt Restriction ◽  
Low Salt ◽  
Blood Pressures ◽  
Renal Vascular ◽  
Rat Kidneys

We examined the responses to the calcium channel blocker, nitrendipine, of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistant (DR) rats that had been stabilized on high- and low-NaCl diets. Blood pressures of high-salt DS rats exceeded those of the other three groups. After norepinephrine vasoconstriction sufficient to increase renal vascular resistance (RVR) by 50%, the superimposition of 10(-5) M nitrendipine increased the glomerular filtration rate (GFR) of high-salt DS rat kidneys by 125% over control values but returned the GFR of high-salt DR kidneys only to control. Nitrendipine superimposition increased the GFR of low-salt DS and DR rat kidneys by 124 and 40% over control values, respectively, and partially restored the RVR toward control. Nitrendipine alone, without norepinephrine, did not affect the GFR or RVR. The persistence within the DS kidney of an exaggerated glomerular circulatory “rebound” response to nitrendipine following the development of hypertension suggests the possibility of a maladaptation of DS kidney cell calcium regulation. The DR kidney manifests a similar response during salt restriction, but this disappears on a high-NaCl diet.

Impact of high salt versus low salt intake on the response of sympathetic baroreflex sensitivity to orthostasis in women with a history of normal pregnancy

2021 ◽  
Author(s):  
Ryosuke Takeda ◽  
Abigail S.L. Stickford ◽  
Stuart A. Best ◽  
Jeung-Ki Yoo ◽  
Sarah L. Hissen ◽  
...  
Keyword(s):  
Baroreflex Sensitivity ◽  
Salt Intake ◽  
Premenopausal Women ◽  
Normal Pregnancy ◽  
High Salt ◽  
Salt Reduction ◽  
Salt Loading ◽  
Low Salt ◽  
History Of ◽  
Head Up Tilt

Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42±3 (SD) yr] were given a standardized isocaloric high salt (250 mEq sodium/day) or low salt (50 mEq sodium/day) diet for 1 week each (~2 months apart with the order randomized), while water intake was ad libitum. Laboratory testing was performed following each high and low salt period in the mid-luteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 minutes) and during a graded head-up tilt (30° for 5 minutes and 60° for 20 minutes). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P<0.05); however, there was no interaction effect (P=0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P=0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.

scholarly journals Salt Intake and All-Cause Mortality in Hemodialysis Patients

2018 ◽  
Vol 48 (2) ◽  
pp. 87-95
Author(s):  
Tatsuyoshi Ikenoue ◽  
Kiyomi Koike ◽  
Shingo Fukuma ◽  
Satoshi Ogata ◽  
Kunitoshi Iseki ◽  
...  
Keyword(s):  
Salt Intake ◽  
Cardiovascular Death ◽  
Hemodialysis Patients ◽  
High Salt ◽  
Salt Restriction ◽  
Data Registry ◽  
High Salt Intake ◽  
Low Salt ◽  
All Cause Mortality ◽  
Registry Database

Background: Although some clinical practice guidelines regarding hemodialysis recommend salt restriction, few studies have examined the association between salt intake and clinical outcomes in hemodialysis patients. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. Methods: This retrospective cohort study was based on the Japanese Society for Dialysis Therapy renal data registry database (2008) and included 88,115 adult patients who had received hemodialysis for at least 2 years. Estimated salt intake was the main predictor and was calculated from intra-dialytic weight loss and pre- and post-dialysis serum sodium levels. Nonlinear logistic regression was used to determine the association between salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cardiovascular death at 1 year. Results: The median (25–75th percentile) salt intake at baseline was 6.4 (4.6–8.3) g/day. At 1 year, all-cause mortality occurred in 1,845 (2.1%) patients, including 807 cardiovascular deaths. The low salt intake group (< 6 g/day) demonstrated the highest all-cause mortality and cardiovascular deaths. No association was observed between high salt intake, all-cause mortality and cardiovascular deaths. The lowest risk for all-cause mortality and cardiovascular death occurred among patients with an estimated salt intake of 9 g/day. Conclusion: Low salt intake, but not high salt intake, was associated with all-cause and cardiovascular mortality in Japanese hemodialysis patients. Further studies to justify including a lower limit of salt intake for hemodialysis patients are suggested.

scholarly journals Low-Salt Diet Attenuates B-Cell- and Myeloid-Cell-Driven Experimental Arthritides by Affecting Innate as Well as Adaptive Immune Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Bettina Sehnert ◽  
Sandy Pohle ◽  
Cornelia Heuberger ◽  
Rita Rzepka ◽  
Maximilian Seidl ◽  
...  
Keyword(s):  
T Cells ◽  
Salt Intake ◽  
Mitogen Activated Protein Kinase ◽  
Chloride Salt ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Effector Phase ◽  
Low Salt ◽  
The Impact ◽  
And Cartilage

A link between high sodium chloride (salt) intake and the development of autoimmune diseases was previously reported. These earlier studies demonstrated exacerbation of experimental autoimmune encephalomyelitis and colitis by excess salt intake associated with Th17- and macrophage-mediated mechanisms. Little is known about the impact of dietary salt intake on experimental arthritides. Here, we investigated if salt restriction can exert beneficial effects on collagen-induced arthritis (CIA) and K/BxN serum transfer-induced arthritis (STIA). CIA depends on both adaptive and innate immunity, while STIA predominantly mimics the innate immune cell-driven effector phase of arthritis. In both models, low salt (LS) diet significantly decreased arthritis severity compared to regular salt (RS) and high salt (HS) diet. We did not observe an aggravation of arthritis with HS diet compared to RS diet. Remarkably, in STIA, LS diet was as effective as IL-1 receptor blocking treatment. Complement-fixing anti-CII IgG2a antibodies are associated with inflammatory cell infiltration and cartilage destruction. LS diet reduced anti-CII IgG2a levels in CIA and decreased the anti-CII IgG2a/IgG1 ratios pointing toward a more Th2-like response. Significantly less inflammatory joint infiltrates and cartilage breakdown associated with reduced protein concentrations of IL-1 beta (CIA and STIA), IL-17 (CIA), and the monocyte chemoattractant protein-1 (MCP-1) (CIA) were detected in mice receiving LS diet compared to HS diet. However, we did not find a reduced IL-17A expression in CD4+ T cells upon salt restriction in CIA. Analysis of mRNA transcripts and immunoblots revealed a link between LS diet and inhibition of the p38 MAPK (mitogen-activated protein kinase)/NFAT5 (nuclear factor of activated T-cells 5) signaling axis in STIA. Further experiments indicated a decreased leukodiapedesis under LS conditions. In conclusion, dietary salt restriction ameliorates CIA and STIA, indicating a beneficial role of LS diet during both the immunization and effector phase of immune-mediated arthritides by predominantly modulating the humoral immunity and the activation status of myeloid lineage cells. Hence, salt restriction might represent a supportive dietary intervention not only to reduce cardiovascular risk, but also to improve human inflammatory joint diseases like rheumatoid arthritis.

The Dietary Guideline with Great Therapeutic Potential

2008 ◽  
Vol 14 (3) ◽  
pp. 120 ◽  
Author(s):  
Trevor C. Beard
Keyword(s):  
Salt Intake ◽  
Therapeutic Potential ◽  
Sodium Content ◽  
Traffic Light ◽  
Salt Restriction ◽  
Food Standards ◽  
Dietary Guideline ◽  
Low Salt ◽  
Portion Sizes ◽  
Definition Of

Prescribing 'salt restriction' for patients with salt-related health problems - using diets measuring sodium content and portion sizes - has been notoriously unpopular and unreliable, and the only therapeutic alternative has been to prescribe diuretics. This article reports a new observation that total salt intake is low enough (sodium < 5 0 mmol/day) to be more effective and less troublesome than diuretics in people who follow the Australian dietary guideline to choose foods low in salt while using the definition of low salt foods in the Australia New Zealand Food Standards Code (Na =120 mg/100g). Low salt foods - eaten exclusively during human evolution - can usually abolish the severe vertigo of Meniere?s disorder as the sole treatment, and reverse the universal rise of blood pressure with age, preventing hypertension. This simple prescription for better food (a healthier salt intake) enables health professionals to obtain measurable and permanent clinical improvement in motivated patients. The full public health potential of better food will require a long period of gradual reform in food processing and the evolution of a new cuisine. Shoppers must know what they are buying, and Australia needs Britain?s traffic light labels that identify low salt foods at a glance with green lights for salt.

Effect of Dietary Salt Restriction on Renal Sensitivity to Vasopressin in Man

1995 ◽  
Vol 89 (1) ◽  
pp. 37-43 ◽  
Author(s):  
M. Sutters ◽  
R. Duncan ◽  
W. S. Peart
Keyword(s):  
Arginine Vasopressin ◽  
Low Dose ◽  
Salt Intake ◽  
Renal Plasma Flow ◽  
High Salt ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Vasopressin Infusion ◽  
Antidiuretic Effect ◽  
Low Salt

1. We have previously described a progressive antidiuresis in response to low-dose vasopressin infusion during salt restriction in man, despite stable or even declining plasma vasopressin concentration. In the present study we examine the hypothesis that renal sensitivity to the antidiuretic effect of arginine vasopressin may be enhanced by salt restriction. 2. Extremely low-dose infusions of arginine vasopressin were given to normal subjects after equilibration to high (260 mmol/day) and low (20 mmol/day) sodium intakes. 3. Salt restriction increased the antidiuretic effect of arginine vasopressin (2 fmol min−1 kg−1 arginine vasopressin increased urine osmolality from 67.8 ± 2.6 to 196.3 ± 35.7 mosmol/l in the high-salt study and from 268.3 ± 49 mosmol/l in the low-salt study; P < 0.05 between sodium intakes). Glomerular filtration rate, estimated from inulin clearance, was unchanged during arginine vasopressin infusion irrespective of salt intake (high salt 116.5 ± 9.4 to 118.9 ± 6.4 ml/min; low salt, 135.1 ± 9.2 to 111.2 ± 12.4 ml/min). Renal plasma flow, estimated from para-aminohippurate clearance, fell further during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study than in the high-salt study (low salt, from 555.7 ± 22.7 to 298.3 ± 27.6 ml/min; high salt, from 544.5 ± 30.2 to 452.9 ± 28.9 ml/min; P < 0.05 between sodium intakes). 4. Plasma atrial natriuretic peptide concentration increased during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study (to 136.5% ± 19.9% of baseline, P < 0.05), if anything falling in the high-salt study (to 90.5% ± 13.6% of baseline). Packed cell volume fell during arginine vasopressin infusion in the low-salt study (high salt, to 98.2% ± 0.4% of baseline; low salt, to 95.7% ± 0.4% of baseline, P < 0.05 for the low-salt study only). 5. Plasma arginine vasopressin concentration was constant throughout each study (high salt 0.48 ± 0.12 to 0.48 ± 0.1 pmol/l; low salt, 0.38 ± 0.05 to 0.4 ± 0.04 pmol/l). 6. Our findings suggest that renal sensitivity to the hydro-osmotic and vascular effects of arginine vasopressin is enhanced by salt restriction.

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