Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake

2011 ◽  
Vol 301 (2) ◽  
pp. F263-F270 ◽  
Author(s):  
M. C. Fiore ◽  
P. M. Jimenez ◽  
D. Cremonezzi ◽  
L. I. Juncos ◽  
N. H. García
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Body Weight ◽  
Salt Intake ◽  
High Salt ◽  
Lipid Lowering ◽  
Inflammatory Factors ◽  
Glomerular Volume ◽  
High Salt Intake ◽  
Tgf Β1

High salt intake (HS) is a risk factor for cardiovascular and kidney disease. Indeed, HS may promote blood-pressure-independent tissue injury via inflammatory factors. The lipid-lowering 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors exert beneficial lipid-independent effects, reducing the expression and synthesis of inflammatory factors. We hypothesized that HS impairs kidney structure and function in the absence of hypertension, and these changes are reversed by atorvastatin. Four groups of rats were treated for 6 wk in metabolic cages with their diets: normal salt (NS); HS, NS plus atorvastatin and HS plus atorvastatin. We measured basal and final body weight, urinary sodium and protein excretion (UProtV), and systolic blood pressure (SBP). At the end of the experimental period, cholesterolemia, creatinine clearance, renal vascular reactivity, glomerular volume, cortical and glomerular endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-β1 expression were measured. We found no differences in SBP, body weight, and cholesterolemia. HS rats had increased creatinine clearence, UProtV, and glomerular volume at the end of the study. Acetylcholine-induced vasodilatation decreased by 40.4% in HS rats ( P < 0.05). HS decreased cortical and glomerular eNOS and caused mild glomerular sclerosis, interstitial mononuclear cell infiltration, and increased cortical expression of TGF-β1. All of these salt-induced changes were reversed by atorvastatin. We conclude that long-term HS induces inflammatory and hemodynamic changes in the kidney that are independent of SBP. Atorvastatin corrected all, suggesting that the nitric oxide-oxidative stress balance plays a significant role in the earlier stages of salt induced kidney damage.

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

2011 ◽  
Vol 110 (2) ◽  
pp. 468-471 ◽  
Author(s):  
Mirian J. Starmans-Kool ◽  
Alice V. Stanton ◽  
Yun Y. Xu ◽  
Simon A. McG Thom ◽  
Kim H. Parker ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Wave Reflection ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake ◽  
Increased Risk

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22–40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60–80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (Pf) and backward (Pb) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (Pb/Pf) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.

Deletion of cyclooxygenase-2 in the mouse increases arterial blood pressure with no impairment in renal NO production in response to chronic high salt intake

2013 ◽  
Vol 304 (10) ◽  
pp. R899-R907 ◽  
Author(s):  
Mette Stæhr ◽  
Pernille B. L. Hansen ◽  
Kirsten Madsen ◽  
Paul M. Vanhoutte ◽  
Rolf M. Nüsing ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Salt Intake ◽  
High Salt ◽  
No Production ◽  
Arterial Blood ◽  
High Salt Intake ◽  
Cox 2

Experiments were designed to test the hypothesis that cyclooxygenase-2 (COX-2) activity attenuates the blood pressure increase during high NaCl intake by stimulation of endothelial nitric oxide synthase (eNOS)-mediated NO synthesis in the kidney medulla. COX-2−/− (C57BL6) an COX-2+/+ mice were fed a diet with 0.004% (low salt, LS) or 4% (high salt, HS) NaCl for 18 days. Arterial blood pressure was recorded continuously using indwelling catheters. Food and water intake and diuresis were measured in metabolic cages. Urine osmolality and excretion of electrolytes, cGMP, cAMP, and NOx were determined, as well as plasma NOx and cGMP. There was a significant dependence of blood pressure on salt intake and genotype: COX-2−/− exhibited higher blood pressure than COX-2+/+ both on HS and LS intake. COX-2+/+ littermates displayed an increase in blood pressure on HS versus LS (102.3 ± 1.1 mmHg vs. 91.9 ± 0.9 mmHg) day and night. The mice exhibited significant blood pressure increases during the awake phase (night) that were larger in COX-2−/− on HS diet compared with COX-2+/+. Water intake, diuresis, Na+, and osmolyte excretions and NOx and cGMP excretions were significantly and similarly elevated with HS in COX-2−/− and COX-2+/+. In summary, C57BL6 mice exhibit a salt intake-dependent increase in arterial blood pressure with increased renal NO production. COX-2 activity has a general lowering effect on arterial blood pressure. COX-2 dampens NaCl-induced increases in arterial blood pressure in the awake phase. In conclusion, COX-2 activity attenuates the changes in nocturnal blood pressure during high salt intake, and COX-2 activity is not necessary for increased renal nitric oxide formation during elevated NaCl intake.

Renal–adrenal interrelationships in experimental hypertension

1968 ◽  
Vol 46 (2) ◽  
pp. 179-188 ◽  
Author(s):  
D. Ostrovsky ◽  
F. R. Papsin ◽  
A. G. Gornall
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Renal Artery ◽  
High Blood Pressure ◽  
Salt Intake ◽  
Renal Tissue ◽  
Experimental Hypertension ◽  
Normal Blood Pressure ◽  
Renal Hypertrophy ◽  
High Salt Intake

For several weeks after partial constriction of one renal artery, the fate of this "clipped" kidney seems to exert a determining influence on blood pressure. Rats that remained hypertensive throughout the experiment almost invariably had clipped kidneys averaging 0.16 to 0.22% of body weight. Below 0.1%, this kidney was usually quite atrophic, and its presence was consistent with falling or normal blood pressure. The untouched kidney in such rats was, on the average, heavier in the hypertensive than in the normotensive animals. Since the latter also had less renal tissue on the clipped side, it appears that factors leading to high blood pressure stimulated hypertrophy beyond the level provoked by renoprival factors. In rats on a high salt intake, 5 μg/day of D-aldosterone for 3 months stimulated significant true renal hypertrophy in the absence of a rise in blood pressure. Such hypertrophy was more pronounced in similar rats that had been getting 250 μg DOCA/day for 3 months but were also normotensive. Rats that developed hypertension on this latter regimen had still heavier kidneys. Renal hypertrophy appears to be a prehypertensive phenomenon which persists and can become even more pronounced in hypertension. The highest levels of renal hypertrophy were usually associated with significant adrenal hypertrophy. Endocrine functions may be involved in renal hypertrophy. This concept is discussed in relation to a phospholipid "renin inhibitor" recently isolated from dog and hog kidneys.

Abstract 142: A Fructose-but Not a Glucose-enriched Diet, Induces a Salt-dependent Increase in Blood Pressure and Enhances NKCC2 Phosphorylation in Normal Rats

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Keyona N King-Medina ◽  
Emily Henson ◽  
Pablo Ortiz
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Salt Intake ◽  
Caloric Intake ◽  
High Salt ◽  
Human Consumption ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
High Fructose ◽  
High Salt Intake

Human consumption of fructose as a sweetener has increased in the past 30 years. High fructose intake has been implicated in the development of hypertension, diabetes, and obesity. In the US, the upper 10th percentile of the population consumes up to 40% of their caloric intake from added sugars, in which fructose represents half of these. Fructose metabolism is strikingly different from that of glucose. Yet, the effect of a fructose or glucose-enriched diet in salt handling by the kidney, affecting blood pressure, and its interaction with high salt intake has been poorly studied. In genetic models of salt-sensitive hypertension, the activity of the Na + /K + /2Cl - cotransporter (NKCC2) in the thick ascending limb (TAL) is abnormally enhanced. We hypothesized that chronic fructose in drinking water induces a salt-dependent increase in blood pressure and stimulates NKCC2 during high salt intake in normal rats. Sprague-Dawley rats were given 20% fructose or 20% glucose in drinking water for 1 week after which a high salt (HS) diet (4% Na + in chow) was started for 3 weeks. When we measured systolic blood pressure (SBP) by tail cuff plethysmography in fructose-fed and glucose-fed rats on a HS diet, only the fructose-fed rats had an increased SBP from 120±10 to 132±6 mmHg on day 7 of HS (p<0.01). SBP continued to increase up to 144±18 mmHg after 3 weeks (p<0.01 vs glucose). Fructose or glucose alone did not increase SBP after 4 weeks. We then repeated the protocol using radiotelemetry to monitor the blood pressure (BP). In rats fed fructose, by day 5 of HS the SBP increased by 12±3 mmHg (p<0.02) and SBP remained elevated for 3 weeks (delta: 10±2.5 mmHg, n=3). In rats fed glucose, a HS diet did not significantly change SBP for 3 weeks (n=5). Moreover, NKCC2 activity in the TAL is enhanced by phosphorylation at Thr96, 101. We found that NKCC2 phosphorylation was higher in rats fed fructose plus HS (p<0.02) but not in rats fed glucose plus HS for 3 weeks (HS: 100, fructose+HS: 250±40%, glucose+HS: 95±10%). Therefore, we conclude that a high fructose (but not a glucose) diet in normal rats induces a salt-dependent increase in BP independently from caloric intake. Thus, the increase in BP may in part be due to the stimulation of NKCC2 phosphorylation in the TAL by fructose.

scholarly journals The Relationship Between Urine Uromodulin and Blood Pressure Changes: The DASH-Sodium Trial

2020 ◽  
Author(s):  
Christine Y Bakhoum ◽  
Cheryl A M Anderson ◽  
Stephen P Juraschek ◽  
Casey M Rebholz ◽  
Lawrence J Appel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Control Diet ◽  
Random Order ◽  
High Salt ◽  
Thick Ascending Limb ◽  
Feeding Period ◽  
High Sodium ◽  
Sodium Diet ◽  
High Salt Intake

Abstract BACKGROUND Uromodulin modulates the sodium-potassium-two-chloride transporter in the thick ascending limb of the loop of Henle, and its overexpression in murine models leads to salt-induced hypertension. We hypothesized that individuals with higher baseline levels of urine uromodulin would have a greater increase in systolic blood pressure (SBP) for the same increase in sodium compared with those with lower uromodulin levels. METHODS We used data from 157 subjects randomized to the control diet of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial who were assigned to 30 days of low (1,500 mg/d), medium (2,400 mg/d), and high salt (3,300 mg/d) diets in random order. Blood pressure was measured prerandomization and then weekly during each feeding period. We evaluated the association of prerandomization urine uromodulin with change in SBP between diets, as measured at the end of each feeding period, using multivariable linear regression. RESULTS Baseline urine uromodulin stratified by tertiles was ≤17.64, 17.65–31.97, and ≥31.98 µg/ml. Across the tertiles, there were no significant differences in SBP at baseline, nor was there a differential effect of sodium diet on SBP across tertiles (low to high, P = 0.81). After adjusting for age, sex, body mass index, and race, uromodulin levels were not significantly associated with SBP change from low to high sodium diet (P = 0.42). CONCLUSIONS In a randomized trial of different levels of salt intake, higher urine uromodulin levels were not associated with a greater increase in blood pressure in response to high salt intake.

scholarly journals Relationship Between Salt Intake and Blood Pressure in Hypertensive Patients in Beijing

2020 ◽  
Vol 33 (4) ◽  
pp. 371-371
Author(s):  
Hong-yi Wang ◽  
Yong-jie He ◽  
Wei Li ◽  
Fan Yang ◽  
Ning-ling Sun
Keyword(s):  
Blood Pressure ◽  
Ambulatory Blood Pressure ◽  
Salt Intake ◽  
Blood Pressure Monitoring ◽  
Urinary Sodium Excretion ◽  
High Salt ◽  
Pressure Monitoring ◽  
Hypertensive Patients ◽  
High Salt Intake ◽  
Tertiary Hospitals

Abstract Background To survey the relationship between salt intake and blood pressure in hypertensive patients in Beijing. Methods A cross-sectional survey was used. Essential hypertensive patients were enrolled and divided into three groups (low, medium, and high salt intake) according to their 24 h urinary sodium excretion, which was used to access the salt intake. Blood pressure was measured through office measurement and ambulatory blood pressure monitoring. Results A total of 2,241 patients were enrolled with a mean age of 59.5 ± 13.8 years, mean blood pressure of 141.1 ± 18.5/84.6 ± 12.7 mm Hg, and urinary sodium excretion of 163.9 (95% CI 160.3–167.4) mmol [equal to salt intake 9.59 (9.38–9.79) g/d]. There were 1,544 cases from tertiary hospitals and the other 697 cases from community hospitals. Patients from community hospitals took more salt than patients from tertiary hospitals. Patients with high salt intake were younger than patients with low and medium salt intake. There were more males in high salt intake group than in the other two groups. Ambulatory blood pressure monitoring showed that patients with high salt intake had higher mean blood pressure not only in daytime, but also at night. The diastolic blood pressure in patients with medium salt intake was higher than that in patients with low salt intake. Conclusions Higher salt intake was associated with higher ambulatory blood pressure in hypertensive patients. More effort should be made to lower salt intake to improve blood pressure control rate.

scholarly journals High Salt Intake Augments Blood Pressure Responses During Submaximal Aerobic Exercise

2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Matthew C. Babcock ◽  
Austin T. Robinson ◽  
Kamila U. Migdal ◽  
Joseph C. Watso ◽  
Christopher R. Martens ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aerobic Exercise ◽  
Salt Intake ◽  
High Salt ◽  
High Salt Intake ◽  
Submaximal Aerobic Exercise ◽  
Blood Pressure Responses

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.

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