Administration of the steroid marinobufagenin (MBG) mimics Salt-Sensitive hypertension in Dahl-S, but not in normotensive Sprague-Dawley rats

Consumption of high-fructose corn syrup as a sweetener has increased dramatically. Fructose has been implicated in the epidemic of diabetes, obesity and hypertension including salt-sensitive hypertension. However, the mechanisms are poorly understood. The proximal nephron reabsorbs 60-70% of the fluid and Na, and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport has been implicated in several forms of hypertension. We hypothesized that fructose stimulates NHE3 activity and enhances the ability of angiotensin II (ANG II) to activate NHE3 in the proximal tubule. To test our hypothesis we isolated and perfused proximal tubules from Sprague Dawley rats. NHE3 activity was measured as the recovery of intracellular pH after an NH4Cl acid pulse using the pH sensitive dye BCECF. The rate of pH recovery was measured in Fluorescent Units per second (FU/sec). In the presence of a 5.5 mM glucose-containing physiological saline the basal rate of pH recovery was 3.1 ± 0.8 FU/sec. When the luminal solution was exchanged to a 0.6 mM glucose + 5 mM fructose-containing physiological saline in a second period, the rate of pH recovery increased to 5 ± 1 FU/sec (p<0.03, n=8).To study whether this effect was due to the addition of fructose or the removal of glucose to the lumen, we performed a separate set of experiments where 5 mM glucose was substituted for 5 mM fructose. In the presence of 0.6 mM glucose the basal rate of pH recovery was 3.6 ± 1.5 FU/sec. When 5 mM fructose was added the rate of pH recovery increased to 5.9 ± 2 FU/sec (p<0.02, n=5). Control experiments showed no differences between periods when 5 mm glucose was added back to the luminal perfusate. Finally, we tested the effect of low concentrations of ANG II in the presence or absence of luminal fructose. In the presence of 5.5 mM glucose, ANG II 10-12 M did not affect the rate of pH recovery (change: -1.1 ± 0.5 FU/sec, n=9). However, in the presence of 5 mM fructose, ANG II increased the rate of pH recovery (change: 4.0 ± 2.2 FU/sec, p< 0.03 n=6). We conclude that acute treatment with fructose stimulates NHE3 activity and enhances the ability of ANG II to activate NHE3 in the proximal tubule. These results may partially explain the mechanism by which a fructose diet induces hypertension.

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Gut dysbiosis contributes to high fructose–induced salt-sensitive hypertension in Sprague-Dawley rats

Nutrition ◽

10.1016/j.nut.2020.110766 ◽

2020 ◽

Vol 75-76 ◽

pp. 110766 ◽

Cited By ~ 1

Author(s):

Yang Chen ◽

Yeyan Zhu ◽

Chunying Wu ◽

Aihua Lu ◽

Mokan Deng ◽

...

Keyword(s):

Sprague Dawley ◽

Gut Dysbiosis ◽

Sprague Dawley Rats ◽

High Fructose ◽

Salt Sensitive Hypertension

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00514.2014 ◽

2016 ◽

Vol 310 (2) ◽

pp. R115-R124 ◽

Cited By ~ 12

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.

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OXIDATIVE STRESS INDUCED RENAL D1 RECEPTOR DYSFUNCTION CAUSES SALT SENSITIVE HYPERTENSION IN SPRAGUE DAWLEY RATS

The FASEB Journal ◽

10.1096/fasebj.20.5.a1184 ◽

2006 ◽

Vol 20 (5) ◽

Author(s):

ANEES AHMAD BANDAY ◽

MUSTAFA F. LOKHANDWALA

Keyword(s):

Oxidative Stress ◽

D1 Receptor ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Salt Sensitive Hypertension

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Corrigendum to

Nutrition ◽

10.1016/j.nut.2020.110845 ◽

2020 ◽

Vol 77 ◽

pp. 110845

Author(s):

Yang Chen ◽

Yeyan Zhu ◽

Chunying Wu ◽

Aihua Lu ◽

Mokan Deng ◽

...

Keyword(s):

Sprague Dawley ◽

Gut Dysbiosis ◽

Sprague Dawley Rats ◽

High Fructose ◽

Salt Sensitive Hypertension

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Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.5.r1070 ◽

1991 ◽

Vol 261 (5) ◽

pp. R1070-R1074 ◽

Cited By ~ 1

Author(s):

K. Ando ◽

Y. Sato ◽

A. Ono ◽

K. Takahashi ◽

T. Shimosawa ◽

...

Keyword(s):

Angiotensin Ii ◽

Antihypertensive Effect ◽

Hypotensive Effect ◽

Plasma Catecholamine ◽

Ang Ii ◽

Sprague Dawley ◽

Calcium Loading ◽

Sprague Dawley Rats ◽

Salt Sensitive Hypertension ◽

Do So

To clarify the hypotensive effect of high dietary Ca intake on salt-sensitive hypertension, 7-wk-old Sprague-Dawley rats, 3.15% Na and/or 4.07% Ca diet loaded, were administered 125 ng/ml of angiotensin II (ANG II) intraperitoneally for 12 days. Compared with control rats (mean blood pressure 108 +/- 2 mmHg), ANG II administration caused hypertension (131 +/- 4 mmHg, P less than 0.05). Na loading enhanced the hypertensive effect of ANG II (161 +/- 4 mmHg, P less than 0.01). Dietary Ca loading did not significantly inhibit the pressor effect of ANG II alone (119 +/- 4 mmHg). However, Ca loading suppressed hypertension in ANG II-salt rats (126 +/- 4 mmHg, P less than 0.01). Plasma total catecholamine (norepinephrine + epinephrine) was increased in ANG II-salt rats (176 +/- 14 vs. 290 +/- 23 pg/ml, P less than 0.05), but Ca loading decreased plasma catecholamine (182 +/- 13 pg/ml, P less than 0.05). In contrast, plasma catecholamine was not significantly different between ANG II-treated rats with and without Ca loading. Ca loading increased serum Ca in ANG II rats (10.9 +/- 0.1 vs. 11.7 +/- 0.1 mg/dl, P less than 0.05) but did not do so significantly in ANG II-salt rats (10.8 +/- 0.2 vs. 10.9 +/- 0.1 mg/dl). Thus Ca loading exclusively ameliorated salt-sensitive hypertension, which was induced with ANG II administration and Na loading in rats, probably through suppression of the increased sympathetic activity. In addition, these effects of Ca loading were not mediated through an increased blood level of Ca.

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Abstract 083: Neurons in the Organum Vasculosum of the Lamina Terminalis Contribute to Salt-sensitive Hypertension

Hypertension ◽

10.1161/hyp.70.suppl_1.083 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Sean D Stocker

Keyword(s):

Salt Intake ◽

Lamina Terminalis ◽

Sprague Dawley ◽

Dietary Salt ◽

Dietary Salt Intake ◽

Arterial Blood ◽

Sprague Dawley Rats ◽

Organum Vasculosum ◽

Salt Sensitive Hypertension

Excess dietary salt intake raises plasma and cerebrospinal fluid NaCl concentrations to elevate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Changes in extracellular NaCl concentrations are sensed by neurons in the organum vasculosum of the lamina terminalis (OVLT) - a circumventricular organ that lacks a complete blood-brain barrier. The purpose of the present study was to investigate the hypothesis that salt-sensitive hypertension was mediated, in part, by an elevated activity of OVLT neurons. Dahl-Salt-Sensitive or Sprague-Dawley rats (8-10 weeks) were fed 0.5% or 4.0% NaCl diets for 3-4 weeks. First, in vivo single-unit recordings demonstrate the discharge of OVLT neurons in Dahl-Salt-Sensitive rats was higher after a 4.0% versus 0.5% NaCl diet (4.1±0.4 Hz vs 1.9±0.3 Hz, n=6 per group, P<0.05). OVLT neuronal discharge of Sprague-Dawley rats was not different after a 4.0% or 0.5% NaCl diet (2.1±0.4 Hz vs 1.7±0.3 Hz, n=6-9 per group, P>0.5). In a second set of experiments, injection of hypertonic NaCl (1.0M NaCl, 20nL) into the OVLT produced significantly greater increases in lumbar SNA (131±6% vs 116±3%, n=4 per group, P<0.05) and mean ABP (14±2 vs 8±2 mmHg, n=4 per group, P<0.05) of Dahl-Salt-Sensitive rats fed 4.0% versus 0.5% NaCl respectively. Sprague-Dawley rats fed 4.0% versus 0.5% NaCl exhibited responses of smaller magnitude for both lumbar SNA (115±4 vs 108±3%, n=4 per group, P<0.05) and mean ABP (9±2 vs 6±2 mmHg, n=4 per group, P<0.05). Interestingly, the duration of the response was much longer in Dahl-Salt-Sensitive versus Sprague-Dawley rats (data not shown). Finally, inhibition of neuronal activity by injection of the GABA agonist muscimol (5mM, 20nL) into the OVLT produced a significantly greater fall in lumbar SNA (-25±4% vs -11±3%, n=4 per group, P<0.05) and mean ABP (-19±4 vs -6±2 mmHg, n=4 per group, P<0.05) of Dahl-Salt-Sensitive rats fed 4.0% versus 0.5% NaCl, respectively. Injection of muscimol into the OVLT of Sprague-Dawley rats did not significantly affect SNA or mean ABP. Collectively, these findings suggest a high salt diet increases the activity of OVLT neurons to elevate SNA and ABP in salt-sensitive hypertension.

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