Proximal tubular fluid, kidney, and plasma levels of angiotensin II in hypertensive ren-2 transgenic rats

1997 ◽  
Vol 273 (2) ◽  
pp. F246-F253 ◽  
Author(s):  
K. D. Mitchell ◽  
S. M. Jacinto ◽  
J. J. Mullins
Keyword(s):  
Left Kidney ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin I ◽  
Transgenic Rats ◽  
A Value ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Fluid Collections ◽  
Normotensive Control

The present study was performed to assess the plasma and kidney levels of angiotensin I (ANG I) and ANG II during prehypertensive (4- to 5-wk old), development (6- to 8-wk old), and maintenance (10- to 12-wk old) phases of hypertension in pentobarbital-anesthetized transgenic rats [TGR; strain name: TGR(mRen2)27] and age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). At 4-5 wk, mean arterial pressures of TGR were not different from those of HanSD (110 +/- 5 vs. 114 +/- 4 mmHg). However, mean arterial pressures of 6-8 wk and 10-12 wk TGR were higher than those of HanSD (179 +/- 3 vs. 110 +/- 6 and 173 +/- 5 vs. 116 +/- 3 mmHg, respectively; P < 0.01 in both cases). Plasma ANG II levels in 4-5 wk and 6-8 wk TGR were not different from those in HanSD (70 +/- 11 vs. 66 +/- 7 and 60 +/- 8 vs. 48 +/- 12 fmol/ml, respectively). However, plasma ANG II levels in 10-12 wk TGR were higher than those in HanSD (125 +/- 26 vs. 38 +/- 12 fmol/ml, P < 0.01). Kidney ANG II levels in 4-5 wk, 6-8 wk, and 10-12 wk TGR averaged 370 +/- 57, 247 +/- 16, and 562 +/- 86 fmol/g, respectively, values not different from those in HanSD. In additional studies performed on 6-8 wk TGR and HanSD, multiple free-flow proximal tubular fluid collections were obtained and pooled for each animal. In these experiments, mean arterial pressures of the 10 TGR and 7 HanSD studied averaged 178 +/- 9 and 129 +/- 3 mmHg (P < 0.01), respectively. The ANG II concentration in proximal tubular fluid obtained from TGR averaged 5.6 +/- 2.1 pmol/ml (n = 10), a value not different from that in proximal tubular fluid collected from HanSD (5.3 +/- 2.8 pmol/ml, n = 7). However, the ANG II contents of the micropunctured left kidney and the nonmicropunctured right kidney of TGR were lower than those in HanSD (690 +/- 95 vs. 1,374 +/- 210 and 659 +/- 119 vs. 1,303 +/- 196 fmol/g, respectively; P < 0.01 in both cases). The present findings indicate that proximal tubular fluid of hypertensive TGR contains nanomolar concentrations of ANG II and that proximal tubular fluid, plasma and kidney ANG II levels in anesthetized hypertensive TGR are not markedly suppressed compared with those in normotensive control rats.

Enhanced renal vascular responsiveness to angiotensin II in hypertensive ren-2 transgenic rats

1999 ◽  
Vol 276 (2) ◽  
pp. F315-F322 ◽  
Author(s):  
Severina M. Jacinto ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Ang Ii ◽  
Peripheral Vascular ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Renin Gene ◽  
Vascular Responsiveness ◽  
Renal Vascular ◽  
Dose Dependent

The present study was performed to evaluate renal vascular responsiveness (RVR) to ANG II in hypertensive transgenic rats [TGR; strain TGR(mRen2)27] harboring the mouse ren-2 renin gene. Renal blood flow (RBF) responses to either intravenous or intrarenal arterial administration of ANG II were assessed in pentobarbital sodium-anesthetized female heterozygous TGR (9–12 wk old) and age-matched transgene-negative Hanover Sprague-Dawley rats (HanSD). Intravenous bolus injections of 15 and 30 ng ANG II elicited dose-dependent increases in mean arterial blood pressure (AP) and decreases in RBF in both TGR and HanSD. However, the magnitude of the increases in AP was greater in TGR than in HanSD (24 ± 1 vs. 17 ± 2 mmHg and 33 ± 2 vs. 25 ± 1 mmHg, respectively, P < 0.05 in both cases). Similarly, the magnitude of the decrease in RBF elicited by intravenous administration of 15 ng of ANG II was greater in TGR than HanSD (−62 ± 3 vs. −52 ± 5%, P < 0.05). Intrarenal arterial administration of 1.5 and 3 ng ANG II did not alter mean AP in either group but elicited larger decreases in RBF in TGR than in HanSD (−24 ± 2 vs. −13 ± 1% and −41 ± 5 vs. −30 ± 2%, respectively, P< 0.05 in both cases). In contrast, intrarenal arterial administration of norepinephrine (40 and 80 ng) elicited smaller decreases in RBF in TGR than in HanSD (−24 ± 3 vs. −40 ± 6% and −51 ± 9 vs. −71 ± 8%, respectively, P < 0.05 in both cases), indicating that TGR do not exhibit a generalized increase in RVR to endogenous vasoconstrictors. Furthermore, the enhanced RVR to ANG II does not appear to reflect an impaired RVR to endogenous vasodilator factors since intrarenal administration of bradykinin and acetylcholine elicited larger increases in RBF in TGR than in HanSD. The present findings indicate that hypertensive TGR exhibit exaggerated renal and peripheral vascular responses to ANG II, which likely contributes to an increased renal and peripheral vascular resistance and thereby to the hypertension in TGR.

ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

2004 ◽  
Vol 286 (5) ◽  
pp. R865-R873 ◽  
Author(s):  
Charlotte Mehlin Sorensen ◽  
Paul Peter Leyssac ◽  
Max Salomonsson ◽  
Ole Skott ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Over Time

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (Pprox), and proximal tubular flow rate (QLP). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl]ED), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 ± 0.3 to 6.0 ± 0.3 ml/min after 5 min (NS) to 5.2 ± 0.2 ml/min after 30 min ( P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 ± 11.0 × 10-5 to 87.1 ± 25.1 × 10-5 Goldblatt units (GU)/ml after 5 min ( P < 0.05) to 158.5 ± 42.9 × 10-5 GU/ml after 30 min ( P < 0.01). GFR, Pprox, and [NaCl]ED all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.

Abstract 493: Impact of Renal Vasoconstriction on the Relationship Between Blood Pressure and Renal Injury in Angiotensin II-induced Hypertensive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aaron J Polichnowski ◽  
Maria Picken ◽  
Jianrui Long ◽  
Geoffrey Williamson ◽  
Karen Griffin ◽  
...  
Keyword(s):  
Renal Injury ◽  
Left Kidney ◽  
Separate Experiment ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Osmotic Minipump ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
The Relationship

Ang II is thought to play a prominent role in the development of hypertension-induced renal disease via BP dependent and independent pathways; however the quantitative relationships between BP and renal injury have not been rigorously examined in Ang II-induced hypertension. The major goals of the present study were to assess: 1) the relationship between BP and renal injury in rats with hypertension induced by Ang II vs. renal mass reduction (RMR) and 2) the pressure-flow relationships in conscious Ang II-infused rats. One group of male Sprague-Dawley rats (Charles River) were implanted with a BP radiotransmitter and 10 days later administered Ang II (n=12; 500 ng/kg/min via osmotic minipump) or subjected to 3/4 RMR via right uninephrectomy + infarction of ∼ 1/2 of the left kidney (RKI, n=5). BP was measured continuously and kidneys were perfused fixed at 6 weeks for the assessment of renal injury. In a separate experiment, MAP and RBF (Transonic) were measured in conscious chronically instrumented rats. After recovery from surgery (∼7 days), baseline MAP and RBF were assessed (∼4 hours @ 200 Hz) on 2 consecutive days. Subsequently, rats were administered Ang II (n=6; 500 ng/kg/min) or saline (n=7; sham) via osmotic minipump and MAP and RBF were again assessed every 2-3 days for 10 days. Despite a higher average systolic BP over 6 weeks in Ang II (174±3 mmHg) vs. RKI (165±6 mmHg) rats, glomerulosclerosis (GS) was higher (p<0.05) in RKI (15±7% out of 100 glomeruli) vs. Ang II (6±1% out of 100 glomeruli) rats. Moreover, the slope of the relationship between BP and %GS (Δ%GS/ΔmmHg) was greater in RKI vs. Ang II rats. Both MAP (98±2 vs. 99±3 mmHg) and RBF (8.1±1vs. 8.2±1 ml/min) were similar at baseline in Ang II and sham rats, respectively. MAP was elevated by day 3 (123±6 mmHg) and further increased to 157±5 mmHg by day 10 in Ang II rats. Conversely, RBF was decreased at day 3 (6.6±0.6 ml/min) and the vasoconstriction persisted over the experimental protocol as RBF further decreased to 5.6±0.7 ml/min at day 10 in Ang II rats. In conclusion, Ang II-induced hypertension is associated with a diminished susceptibility to renal injury as compared to rats with RMR likely due, in part, to the AngII-induced vasoconstriction, which reduces BP transmission to the renal microvasculature.

scholarly journals Resetting of exaggerated tubuloglomerular feedback activity in acutely volume-expanded young SHR

1999 ◽  
Vol 276 (3) ◽  
pp. F409-F416 ◽  
Author(s):  
Kristina Brännström ◽  
William J. Arendshorst
Keyword(s):  
Turning Point ◽  
Tubuloglomerular Feedback ◽  
Maximal Response ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Wistar Kyoto ◽  
Tubular Flow

One purpose of the present study was to evaluate the ability of 7-wk-old spontaneously hypertensive rats (SHR) to reset tubuloglomerular feedback (TGF) activity in response to acute volume expansion (VE). Second, we evaluated the contribution of ANG II, via its action on AT1 receptors, to TGF control of glomerular function during VE. TGF was assessed by micropuncture methods and proximal tubular stop-flow pressure (SFP) determinations in SHR, Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD). During euvolemia SHR exhibited enhanced TGF activity. In the same animals acute VE was achieved by infusion of saline (5 ml ⋅ h−1 ⋅ 100 g body wt−1). VE led to resetting of TGF in all three strains. Maximal SFP responses, elicited by a 30–40 nl/min loop of Henle perfusion rate, decreased from 19 to 12 mmHg in SHR and, on average, from 11 to 5 mmHg in WKY and SD ( P < 0.001). Tubular flow rate producing a half-maximal response (turning point) shifted to higher flow rates during VE, from 12 to 14 nl/min in SHR and from 15 to 19 nl/min in WKY. Administration of the AT1 receptor blocker candesartan (0.05 mg/kg iv) during sustained VE decreased TGF-mediated reductions in SFP in SHR and slightly increased the turning point in WKY. Nevertheless, other parameters of TGF activity were unaffected by AT1 receptor blockade. In conclusion, young SHR possess the ability to reset TGF activity in response to VE to a degree similar to compensatory adjustments in WKY. However, TGF remains enhanced in SHR during VE. ANG II and its action on AT1 receptors are in part responsible for the exaggerated SFP responses in young SHR during VE.

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.

Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Luciana C Veiras ◽  
Jiyang Han ◽  
Donna L Ralph ◽  
Alicia A McDonough
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Weight Ratio ◽  
Distal Tubule ◽  
Reduce Blood Pressure ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
K Secretion ◽  
Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

Renal endothelin in chronic angiotensin II hypertension

2002 ◽  
Vol 283 (1) ◽  
pp. R243-R248 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Sodium Intake ◽  
Renal Tissue ◽  
High Salt ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Saline Vehicle

To determine the influence of chronic ANG II infusion on urinary, plasma, and renal tissue levels of immunoreactive endothelin (ET), ANG II (65 ng/min) or saline vehicle was delivered via osmotic minipump in male Sprague-Dawley rats given either a high-salt diet (10% NaCl) or normal-salt diet (0.8% NaCl). High-salt diet alone caused a slight but not statistically significant increase (7 ± 1%) in mean arterial pressure (MAP). MAP was significantly increased in ANG II-infused rats (41 ± 10%), and the increase in MAP was significantly greater in ANG II rats given a high-salt diet (59 ± 1%) compared with the increase observed in rats given a high-salt diet alone or ANG II infusion and normal-salt diet. After a 2-wk treatment, urinary excretion of immunoreactive ET was significantly increased by ∼50% in ANG II-infused animals and by over 250% in rats on high-salt diet, with or without ANG II infusion. ANG II infusion combined with high-salt diet significantly increased immunoreactive ET content in the cortex and outer medulla, but this effect was not observed in other groups. In contrast, high-salt diet, with or without ANG II infusion, significantly decreased immunoreactive ET content within the inner medulla. These data indicate that chronic elevations in ANG II levels and sodium intake differentially affect ET levels within the kidney and provide further support for the hypothesis that the hypertensive effects of ANG II may be due to interaction with the renal ET system.

Angiotensin II-mediated biphasic regulation of proximal tubular Na+/H+ exchanger 3 is impaired during oxidative stress

2011 ◽  
Vol 301 (2) ◽  
pp. F364-F370 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Tap Water ◽  
Buthionine Sulfoximine ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Sprague Dawley ◽  
High Concentration ◽  
Nitric Oxide Signaling ◽  
Proximal Tubular

Angiotensin (ANG) II via AT1 receptors (AT1Rs) maintains sodium homeostasis by regulating renal sodium transporters including Na+/H+ exchanger 3 (NHE3) in a biphasic manner. Low-ANG II concentration stimulates whereas high concentrations inhibit NHE3 activity. Oxidative stress has been shown to upregulate AT1R function that could modulate the ANG II-mediated NHE3 regulation. This study was designed to identify the signaling pathways responsible for ANG II-mediated biphasic regulation of proximal tubular NHE3 and the effect of oxidative stress on this phenomenon. Male Sprague-Dawley rats were chronically treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol in tap water for 3 wk. BSO-treated rats exhibited oxidative stress and high blood pressure. At low concentration (1 pM) ANG II increased NHE3 activity in proximal tubules from all animals. However, in BSO-treated rats, the stimulation was more robust and was normalized by tempol treatment. ANG II (1 pM)-mediated NHE3 activation was abolished by AT1R blocker, intracellular Ca2+ chelator, and inhibitors of phospholipase C (PLC) and Ca2+-dependent calmodulin (CaM) but it was insensitive to Giα and protein kinase C inhibitors or AT2R antagonist. A high concentration of ANG II (1 μM) inhibited NHE3 activity in control and tempol-treated rats. However, in BSO-treated rats, ANG II (1 μM) continued to induce NHE3 stimulation. Tempol restored the inhibitory effect of ANG II (1 μM) in BSO-treated rats. The inhibitory effect of ANG II (1 μM) involved AT1R-dependent, cGMP-dependent protein kinase (PKG) activation and was independent of AT2 receptor and nitric oxide signaling. We conclude that ANG II stimulates NHE3 via AT1R-PLC-CaM pathway and inhibits NHE3 by AT1R-PKG activation. Oxidative stress impaired ANG II-mediated NHE3 biphasic response in that stimulation was observed at both high- and low-ANG II concentration.

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.

Angiotensin II releases 20-HETE from rat renal microvessels

2000 ◽  
Vol 279 (3) ◽  
pp. F544-F551 ◽  
Author(s):  
Kevin D. Croft ◽  
John C. McGiff ◽  
Alicia Sanchez-Mendoza ◽  
Mairead A. Carroll
Keyword(s):  
Chemical Ionization ◽  
Ang Ii ◽  
Sprague Dawley ◽  
The Third ◽  
Sprague Dawley Rats ◽  
Vascular Segment ◽  
Effector Unit ◽  
Gas Chromatography Mass Spectroscopy ◽  
Renal Vascular ◽  
Cytochrome P 450

We studied hydroxyeicosatetraenoic acid (HETE) release in response to ANG II from preglomerular microvessels (PGMVs), the vascular segment governing changes in renal vascular resistance. PGMVs were isolated from Sprague-Dawley rats and incubated with NADPH and hormones at 37°C. Eicosanoids were extracted, and cytochrome P-450 (CYP)-derived HETEs were purified and quantitated by negative chemical ionization gas chromatography-mass spectroscopy. PGMVs produced primarily 20- and 19-HETEs, namely, 7.9 ± 1.7 and 2.2 ± 0.5 ng/mg protein, respectively. ANG II (5 nM) increased CYP-HETE release by two- to threefold; bradykinin, phenylephrine, and Ca2+ionophore were without effect. [Sar1]ANG II (0.1–100 μM) dose dependently stimulated 19- and 20-HETEs, an effect blocked by the AT2-receptor antagonist PD-123319 as well as by U-73122, a phospholipase C inhibitor. Microvascular 20-HETE release was increased more than twofold by the third day in response to ANG II (120 ng · kg−1 · min−1) infused subcutaneously for 2 wk; it was not further enhanced after 14 days, although blood pressure continued to rise. Thus an AT2-phospholipse C effector unit is associated with synthesis of a vasoconstrictor product, 20-HETE, in a key renovascular segment.

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