High-salt diet depresses acetylcholine reactivity proximal to NOS activation in cerebral arteries

2002 ◽  
Vol 283 (1) ◽  
pp. H353-H363 ◽  
Author(s):  
Francis A. Sylvester ◽  
David W. Stepp ◽  
Jefferson C. Frisbee ◽  
Julian H. Lombard
Keyword(s):  
Salt Intake ◽  
Cerebral Arteries ◽  
High Salt ◽  
Receptor Expression ◽  
Dietary Salt ◽  
No Donor ◽  
Dietary Salt Intake ◽  
No Release ◽  
Type 3 ◽  
Cytochrome P 450

Rats were fed a low-salt (LS; 0.4% NaCl) or high-salt (HS; 4.0% NaCl) diet for 3 days, and the responses of isolated cerebral arteries to acetylcholine (ACh), the nitric oxide (NO)-dependent dilator bradykinin, and the NO donor 6-(2-hydroxy-1-methyl-2-nitrosohydrazino)- N-methyl-1-hex-anamine (NOC-9) were determined. ACh-induced vasodilation and NO release, assessed with the fluorescent NO indicator 4,5-diaminofluorescein (DAF-2) diacetate, were eliminated with the HS diet. Inhibition of cyclooxygenase, cytochrome P-450 epoxygenase, and acetylcholinesterase did not alter ACh responses. Bradykinin and NOC-9 caused a similar dilation in cerebral arteries of all groups. Arteries from animals on LS or HS diets exhibited similar levels of basal superoxide (O[Formula: see text]) production, assessed by dihydroethidine fluorescence, and ACh responses were unaffected by O[Formula: see text] scavengers. Muscarinic type 3 receptor expression was unaffected by dietary salt intake. These results indicate that 1) a HS diet attenuates ACh reactivity in cerebral arteries by inhibiting NO release, 2) this attenuation is not due to production of a cyclooxygenase-derived vasoconstrictor or elevated O[Formula: see text] levels, and 3) alteration(s) in ACh signaling are located upstream from NO synthase.

Effects of high-salt diet on CYP450-4A ω-hydroxylase expression and active tone in mesenteric resistance arteries

2005 ◽  
Vol 288 (4) ◽  
pp. H1557-H1565 ◽  
Author(s):  
Jingli Wang ◽  
Richard J. Roman ◽  
John R. Falck ◽  
Lourdes de la Cruz ◽  
Julian H. Lombard
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Resistance Arteries ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Vasoconstrictor Response ◽  
Cytochrome P 450

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po2 after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po2 that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

Exacerbation of central baroreflex impairment in Dahl rats by high-salt diets

1987 ◽  
Vol 252 (2) ◽  
pp. H402-H409 ◽  
Author(s):  
E. Miyajima ◽  
R. D. Bunag
Keyword(s):  
Salt Intake ◽  
Splanchnic Nerve ◽  
Aortic Pressure ◽  
High Salt ◽  
Dietary Salt ◽  
Nerve Activity ◽  
Drug Induced ◽  
Dietary Salt Intake ◽  
Reflex Arc ◽  
Induced Changes

To determine whether baroreflex impairment progresses in hypertensive Dahl rats, we recorded reflex responses to drug-induced changes in blood pressure in hypertension-sensitive (DS) and hypertension-resistant (DR) rats maintained on low- or high-salt diets for 7 wk. Chronotropic responses, manifested as either bradycardia for phenylephrine or tachycardia for sodium nitroprusside, were always smaller in awake DS rats on high-salt diet than in any others. When the same rats were later anesthetized, related changes in afferent aortic and efferent splanchnic nerve activity were similarly reduced. Regardless of dietary salt intake, reflex bradycardia elicited by electrical stimulation of aortic nerve afferents was also weaker in DS than in DR rats, but attendant decreases in mean aortic pressure and splanchnic nerve activity did not differ significantly. These results are compatible with an impairment of afferent and central components of the reflex arc. Even though exact sites of dysfunction were not identified, our findings suggest that in hypertensive DS rats high-salt diets may aggravate baroreflex impairment, at least in part, by acting centrally.

Limitation of arteriolar myogenic activity by local nitric oxide: segment-specific effect of dietary salt

1999 ◽  
Vol 277 (5) ◽  
pp. H1946-H1955 ◽  
Author(s):  
Timothy R. Nurkiewicz ◽  
Matthew A. Boegehold
Keyword(s):  
Nitric Oxide ◽  
Salt Intake ◽  
Specific Effect ◽  
High Salt ◽  
Myogenic Response ◽  
Dietary Salt ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
High Salt Intake ◽  
Wistar Kyoto

The purpose of this study was to determine if local nitric oxide (NO) activity attenuates the arteriolar myogenic response in rat spinotrapezius muscle. We also investigated the possibility that hypertension, dietary salt, or their combination can alter any influence of local NO on the myogenic response. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) fed low-salt (0.45%, LS) or high-salt (7%, HS) diets were enclosed in a ventilated airtight box with the spinotrapezius muscle exteriorized for intravital microscopy. Mean arterial pressure was unaffected by dietary salt in WKY but was significantly higher and augmented by dietary salt in SHR. In all experiments, elevation of microvascular pressure by box pressurization caused a 0–30% decrease in the diameter of large (arcade bridge) arterioles and a 21–27% decrease in the diameter of intermediate (arcade) arterioles. Inhibition of NO synthase with N G-monomethyl-l-arginine (l-NMMA) significantly enhanced myogenic responsiveness of arcade bridge arterioles in WKY-LS and SHR-LS but not in WKY-HS and SHR-HS.l-NMMA significantly enhanced the myogenic responsiveness of arcade arterioles in all four groups. Excess l-arginine reversed this effect of l-NMMA in all cases, and arteriolar responsiveness to the NO donor sodium nitroprusside was not different among the four groups. High-salt intake had no effect on the passive distension of arterioles in either strain during box pressurization. We conclude that 1) local NO normally attenuates arteriolar myogenic responsiveness in WKY and SHR, 2) dietary salt impairs local NO activity in arcade bridge arterioles of both strains, and 3) passive arteriolar distensibility is not altered by a high-salt diet in either strain.

scholarly journals Impaired relaxation of cerebral arteries in the absence of elevated salt intake in normotensive congenic rats carrying the Dahl salt-sensitive renin gene

2010 ◽  
Vol 299 (6) ◽  
pp. H1865-H1874 ◽  
Author(s):  
Matthew J. Durand ◽  
Carol Moreno ◽  
Andrew S. Greene ◽  
Julian H. Lombard
Keyword(s):  
Methyl Ester ◽  
Salt Intake ◽  
Cerebral Arteries ◽  
Brown Norway ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Vascular Relaxation ◽  
Dietary Salt ◽  
Chromosome 13 ◽  
Dietary Salt Intake ◽  
Congenic Strains

This study evaluated endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in isolated middle cerebral arteries (MCA) from Dahl salt-sensitive (Dahl SS) rats and three different congenic strains that contain a portion of Brown Norway (BN) chromosome 13 introgressed onto the Dahl SS genetic background through marker-assisted breeding. Two of the congenic strains carry a 3.5-Mbp portion and a 2.6-Mbp portion of chromosome 13 that lie on opposite sides of the renin locus, while the third contains a 2.0-Mbp overlapping region that includes the BN renin allele. While maintained on a normal salt (0.4% NaCl) diet, MCAs from Dahl SS rats and the congenic strains retaining the Dahl SS renin allele failed to dilate in response to ACh, whereas MCAs from the congenic strain carrying the BN renin allele exhibited normal vascular relaxation. In congenic rats receiving the BN renin allele, vasodilator responses to ACh were eliminated by nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester, angiotensin-converting enzyme inhibition with captopril, and AT1 receptor blockade with losartan. NG-nitro-l-arginine methyl ester-sensitive vasodilation in response to ACh was restored in MCAs of Dahl SS rats that received either a 3-day infusion of a subpressor dose of angiotensin II (3 ng·kg−1·min−1 iv), or chronic treatment with the superoxide dismutase mimetic tempol (15 mg·kg−1·day−1). These findings indicate that the presence of the Dahl SS renin allele plays a crucial role in endothelial dysfunction present in the cerebral circulation of the Dahl SS rat, even in the absence of elevated dietary salt intake, and that introgression of the BN renin allele rescues endothelium-dependent vasodilator responses by restoring normal activation of the renin-angiotensin system.

scholarly journals High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

2013 ◽  
Vol 81 (6) ◽  
pp. 2258-2267 ◽  
Author(s):  
Jennifer A. Gaddy ◽  
Jana N. Radin ◽  
John T. Loh ◽  
Feng Zhang ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Content Type ◽  
Dietary Salt Intake ◽  
Regular Diet ◽  
H Pylori

ABSTRACTPersistent colonization of the human stomach withHelicobacter pyloriis a risk factor for gastric adenocarcinoma, andH. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT)cagA+H. pyloristrain or an isogeniccagAmutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with thecagAmutant strain (P< 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with thein vitroresults, we detected increasedcagAtranscriptionin vivoin animals fed a high-salt diet compared to those on a regular diet. Animals infected with thecagAmutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects ofcagA+H. pyloristrains.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

Cardiology ◽  
2015 ◽  
Vol 130 (4) ◽  
pp. 242-248 ◽  
Author(s):  
Yang Wang ◽  
Dan Wang ◽  
Chao Chu ◽  
Jian-Jun Mu ◽  
Man Wang ◽  
...  
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Potassium ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Potassium Intake ◽  
Potassium Supplementation ◽  
Low Salt

Objective: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Methods: Forty-two subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Results: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. Conclusions: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.

Abstract MP22: Dietary Salt Restriction And High Salt Intake Exaggerate Sympathetic Reflexes And Sensitize Central Autonomic Networks: Potential Mechanisms Of The J-shaped Curve

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Megan M Wenner ◽  
William B Farquhar
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Cardiovascular Responses ◽  
Cardiovascular Morbidity ◽  
High Salt ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Autonomic Networks

Observational cohort studies suggest that severe salt restriction increases cardiovascular morbidity/mortality, and the relationship between cardiovascular morbidity and dietary salt intake resembles a J-shaped curve. A high salt diet exaggerates sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses to several cardiovascular reflexes in salt-resistant animals. This study assessed whether salt restriction also exaggerates cardiovascular reflex responses and sensitizes central autonomic networks. To test this hypothesis, male Sprague-Dawley rats were fed low (0.01% NaCl), normal (0.1% NaCl), and high (4.0% NaCl) salt diet for 14-21 days. Baseline mean ABP was not different across groups (low: 104±4, normal: 107±4, high: 107±4mmHg). Activation of sciatic afferents (1ms pulse, 500uA, 5s duration, 2-20Hz) produced significantly greater increases in renal SNA (5Hz; low: 196±12, normal: 136±9, high: 177±8%, n=8, P<0.05) and ABP (5Hz; low: 29±3, normal: 16±1, high: 24±2 mmHg, n=8, P<0.05) of rats fed low and high versus normal NaCl diets. Activation of the aortic depressor nerve (2ms pulse, 500uA, 15s duration, 2-20Hz) produced significantly greater decreases in renal SNA (5Hz; low: -55±9, normal: -34±8, high: -63±13%, n=7-8, P<0.05) and ABP (5Hz; low: -31±3, normal: -15±5, high: -32±5 mmHg, n=7-8, P<0.05) of rats fed low and high versus normal NaCl diets. To test whether dietary salt intake sensitized central sympathetic circuits, microinjection of L-glutamate (0.1-1nmol, 30nL) in the rostral ventrolateral medulla produced significantly greater increases in renal SNA (0.1nmol; low: 212±15, normal: 149±8, high: 183±17%, n=7-8, P<0.05) and ABP (0.1Hz; low: 20±2, normal: 12±2, high: 22±2 mmHg, n=7-8, P<0.05) of rats fed low and high versus normal NaCl diets. Finally, rats fed low or high NaCl versus normal NaCl diets displayed exaggerated cardiovascular responses to cage switch or mild restraint and increased 24-h blood pressure variability. The present findings show that severe salt restriction and excess dietary salt intake exaggerate sympathetic and cardiovascular responses, and may be explained by a parallel change in the sensitivity of central autonomic networks to resemble a J-shaped curve.

Regulation ofP-450 4A activity in the glomerulus of the rat

1999 ◽  
Vol 276 (6) ◽  
pp. R1749-R1757 ◽  
Author(s):  
Osamu Ito ◽  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Salt Intake ◽  
High Salt ◽  
Dependent Manner ◽  
Hydroxyeicosatetraenoic Acid ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Low Salt

We recently reported that an enzyme of the cytochrome P-450 4A family is expressed in the glomerulus, but there is no evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) can be produced by this tissue. The purpose of present study was to determine whether glomeruli isolated from the kidney of rats can produce 20-HETE and whether the production of this metabolite is regulated by nitric oxide (NO) and dietary salt intake. Isolated glomeruli produced 20-HETE, dihydroxyeicosatrienoic acids, and 12-hydroxyeicosatetraenoic acid (4.13 ± 0.38, 4.20 ± 0.38, and 2.10 ± 0.20 pmol ⋅ min−1⋅ mg protein−1, respectively) when incubated with arachidonic acid (10 μM). The formation of 20-HETE was dependent on the availability of NADPH and the[Formula: see text] of the incubation medium. The formation of 20-HETE was inhibited by NO donors in a concentration-dependent manner. The production of 20-HETE was greater in glomeruli isolated from the kidneys of rats fed a low-salt diet than in kidneys of rats fed a high-salt diet (5.67 ± 0.32 vs. 2.83 ± 0.32 pmol ⋅ min−1⋅ mg protein−1). Immunoblot experiments indicated that the expression of P-450 4A protein in glomeruli from the kidneys of rats fed a low-salt diet was sixfold higher than in kidneys of rats fed a high-salt diet. These results indicate that arachidonic acid is primarily metabolized to 20-HETE and dihydroxyeicosatrienoic acids in glomeruli and that glomerular P-450 activity is modulated by NO and dietary salt intake.

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

1987 ◽  
Vol 73 (6) ◽  
pp. 645-651 ◽  
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.

Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases

2005 ◽  
Vol 85 (2) ◽  
pp. 679-715 ◽  
Author(s):  
Pierre Meneton ◽  
Xavier Jeunemaitre ◽  
Hugh E. de Wardener ◽  
Graham A. Macgregor
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Salt Intake ◽  
Causal Link ◽  
Left Ventricular ◽  
High Salt ◽  
Human Populations ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

Sign in / Sign up

Export Citation Format

Share Document