Abstract 41: Fructose Stimulates Na/H Exchanger 3 Activity and Enhances the Ability of Angiotensin II to Activate Na/H Exchanger 3 in the Proximal Tubule

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pablo Cabral ◽  
Nancy Hong ◽  
Jeffrey Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Physiological Saline ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Basal Rate ◽  
Low Concentrations ◽  
Sprague Dawley Rats ◽  
High Fructose ◽  
Salt Sensitive Hypertension

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.

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

1991 ◽  
Vol 261 (5) ◽  
pp. R1070-R1074 ◽  
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.

Abstract 304: A Moderately- Enriched Fructose Diet Increases The Sensitivity Of The Proximal Nephron To Angiotensin II.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Agustin Gonzalez-Vicente ◽  
Nancy J Hong ◽  
Pablo D Cabral ◽  
Jeffrey L Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Water Reabsorption ◽  
Angiotensin System ◽  
Receptor Mrna ◽  
High Fructose ◽  
Dietary Fructose ◽  
Salt Sensitive Hypertension

Consumption of high-fructose corn syrup as a sweetener has been implicated in diabetes, obesity, and hypertension. We have recently shown that a moderately-enriched fructose diet (20%), an amount consumed by more than 30 million Americans, causes salt-sensitive hypertension. Activation of the renin-angiotensin system in the proximal nephron also increases blood pressure presumably due to augmented salt and water reabsorption. However, whether the effects of angiotensin II (Ang II) on proximal tubule transport are enhanced by moderate fructose consumption is unknown. We hypothesize that a diet containing moderate amounts of fructose increases transport in proximal tubules by enhancing their sensitivity to Ang II. To test this, we measured the effects of Ang II on transport-related oxygen consumption (QO2) in proximal tubule suspensions from rats consuming 20% of their calories as fructose in their drinking water for 1 week. We found that 1 pmol/l Ang II stimulated QO2 by tubules from the fructose-fed group but had no effect on those from controls (21 ± 7 vs. 5 ± 3 nmol/mg/min; p < 0.04, n = 7). In contrast, basal QO2 rates were not affected (94 ± 1 vs. 95 ± 4 nmol O2/mg/min, n = 7). Addition of 100 pmol/l Ang II stimulated QO2 to the same extent in both groups (19 ± 8 vs. 18 ± 8 nmol O2/mg/min; n = 7). AT1 receptor mRNA expression in cortical homogenates was not different between groups (8961 ± 454 vs. 8712 ± 575 AU; n = 4). Both groups gained weight at the same rate. We conclude that moderate dietary fructose consumption increases the sensitivity of the proximal nephron to Ang II independently of AT1 expression, and this may contribute to the salt sensitivity of this model.

scholarly journals Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

2010 ◽  
Vol 298 (1) ◽  
pp. F177-F186 ◽  
Author(s):  
Anne D. M. Riquier-Brison ◽  
Patrick K. K. Leong ◽  
Kaarina Pihakaski-Maunsbach ◽  
Alicia A. McDonough
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Volume Flow Rate ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Associated Proteins ◽  
Gradient Fractionation

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na+/H+ exchanger isoform 3 (NHE3), Na+/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 μg/min for 20 min) that increased PT flow rate ∼20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng·kg−1·min−1 for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H+-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

2007 ◽  
Vol 292 (2) ◽  
pp. F861-F867 ◽  
Author(s):  
Melvin R. Hayden ◽  
Nazif A. Chowdhury ◽  
Shawna A. Cooper ◽  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Proximal Tubule ◽  
Structural Damage ◽  
Kidney Tissue ◽  
Proximal Tubule Cell ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

Mechanism of the biphasic arteriolar response to angiotensin II

1984 ◽  
Vol 247 (1) ◽  
pp. H88-H94 ◽  
Author(s):  
J. T. Fleming ◽  
I. G. Joshua
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin Synthesis ◽  
Krebs Solution ◽  
Ang Ii ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
Third Order ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Alpha Chloralose

Male Sprague-Dawley rats (140-180 g) were anesthetized with alpha-chloralose and urethan. The cremaster muscle with intact blood supply and neural innervation was suspended in a tissue bath containing a modified Krebs solution. With the use of television microscopy the luminal diameters of third-order arterioles (14-32 micron) were measured before and after adding angiotensin II (ANG II, bath concn 10(-6) M). The arterioles responded to ANG II with an initial, transient constriction followed by a more prolonged dilation to a diameter larger than the control diameter. Pretreating the muscle with [Sar1, Ile8]ANG II significantly attenuated both the arteriolar constriction and subsequent dilation induced by ANG II. Treatment of the cremaster muscle with mefenamic acid or indomethacin, inhibitors of prostaglandin synthesis, produced a significant reduction in the diameter of the arterioles and abolished the dilator phase of the arteriolar response to ANG II without preventing the ANG II-induced constriction. These results demonstrate that within the intact microcirculation, ANG II produces both an arteriolar constriction and a dilation that are mediated by specific ANG II receptors. The ANG II-induced dilation of the arterioles appears to be caused by increased prostaglandin synthesis and release.

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

Nutrition ◽  
2020 ◽  
Vol 75-76 ◽  
pp. 110766 ◽  
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

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.

Corrigendum to

Nutrition ◽  
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

Abstract 600: Intrarenal Ghrelin Receptor Antagonism Inhibits cAMP Mediated Angiotensin II Sodium Reabsorption in Normal Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Shetal H Padia
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Ghrelin Receptor ◽  
Sprague Dawley Rats ◽  
Ghrelin Receptors ◽  
Messenger System

An interaction between angiotensin II (Ang II) and ghrelin has been established in many tissues relevant to cardiovascular control, but nothing is known about their relationship within the kidney. Intrarenal ghrelin receptors (GRs) localize to the collecting duct (CD) where they couple to an adenylyl cyclase second messenger system to increase cAMP and ENaC-dependent Na+ reabsorption. Ang II also stimulates the activity of ENaC in the CD (independent of aldosterone), via actions at AT1Rs. The following studies seek to determine whether CD GRs are an important mechanism of Ang II-induced antinatriuresis. Uninephrectomized Sprague-Dawley rats received 3 cumulative 1h renal interstitial (RI) infusions of vehicle 5% dextrose in water (D5W, N=8), Ang II (2 ng/kg/min, N=8), Ang II + D-LYS-GHRP-6, a highly selective GR antagonist (D-LYS, 2, 4, 6 μg/min, N=8) or D-LYS alone (N=8). Urine Na+ excretion rate (UNaV) was measured each hour and compared to baseline, during which only vehicle was infused. RI fluid was collected each hour for cAMP determinations. RI Ang II induced a significant antinatriuresis (UNaV was reduced by 34% at 1h, P<0.01; by 46% at 2h, P<0.001; and by 56% at 3h, P<0.001 from baseline). Ang II-induced antinatriuresis was accompanied by a significant increase in RI cAMP levels from a baseline value of 2.97±0.56 pmol/mL to 10.9±2.2, 13.4±2.2, and 15.3±2.7 pmol/mL after 1h, 2h, and 3h respectively (all P<0.01). However, each of these effects of RI Ang II infusion was abolished by concurrent GR blockade with D-LYS. These data suggest that intact intrarenal GR activity is necessary for Ang II-induced Na+ reabsorption in vivo. Furthermore, since cAMP fails to increase in response to Ang II when GRs are blocked, (and GRs are known to signal via cAMP in the kidney), these data strongly suggest that one of the mechanisms of Ang II-induced Na+ reabsorption in the kidney is via GR-induced increases in cAMP.

Circulating angiotensin II and drinking behavior in rats

1990 ◽  
Vol 259 (3) ◽  
pp. R531-R538 ◽  
Author(s):  
C. M. Pawloski ◽  
G. D. Fink
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Dose Range ◽  
Drinking Behavior ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Physiological Conditions ◽  
Water Drinking ◽  
Sprague Dawley Rats ◽  
Before And After

This study was designed to investigate the effects on water drinking of acute and chronic increases in circulating angiotensin II (ANG II) concentrations in rats. Experiments were conducted in male Sprague-Dawley rats chronically instrumented with femoral arterial and venous catheters and permanently housed in metal metabolism cages. ANG II was infused intravenously either acutely (30 min-2 h) or chronically (3 days) in a dose range of 10-60 ng/min. In no instance did such infusions cause a statistically significant increase in water intake. Other experiments examined the influence of ANG II (10 ng/min iv) on drinking elicited by infusion of hypertonic sodium chloride (1.5 M at 3.5 microliters/min). ANG II administration did not increase drinking to a hypertonic saline stimulus or lower the osmotic threshold for drinking. Nitroprusside (12 micrograms/min) was infused for 30 min to produce hypotension and drinking. Water intake associated with this stimulus was not changed by blocking ANG II formation with enalapril (2 mg/kg iv) or by concomitant infusion of ANG II (10 ng/min iv). Finally, plasma ANG II concentrations were measured before and after 1-h intravenous infusion of saline or ANG II to determine the levels of circulating ANG II produced by the infusion rates used here. It is concluded that the range of circulating ANG II concentrations found under most physiological conditions in rats does not directly stimulate drinking or participate importantly in osmotic or hypotension-induced drinking.

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