Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. R410-R417 ◽  
Author(s):  
Atsushi Sakima ◽  
Hiroshi Teruya ◽  
Masanobu Yamazato ◽  
Rijiko Matayoshi ◽  
Hiromi Muratani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
High Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
Air Jet ◽  
Sd Rats ◽  
Low Salt ◽  
The Brain

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg ⋅ kg−1 ⋅ day−1of N G-monomethyl-l-arginine (l-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 ± 3 mmHg vs. 114 ± 3, 113 ± 1, and 108 ± 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats givenl-NMMA than in rats given aCSF (29 ± 4% vs. 19 ± 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats givenl-NMMA than in rats given aCSF irrespective of salt intake, although the difference was ∼7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.

scholarly journals Modulation of Plasma Sphingosine-1-phosphate Levels via Dietary Salt Intervention in Chinese Adults: An Intervention Trial

2020 ◽  
Author(s):  
Qiong Ma ◽  
Chao Chu ◽  
Yanbo Xue ◽  
Yu Yan ◽  
Jiawen Hu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Repeated Measures ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
Chinese Adults ◽  
Salt Diet ◽  
Low Salt ◽  
Sphingosine 1 Phosphate ◽  
Pressure Modulation

Abstract Background: Salt is a crucial factor for blood pressure modulation, especially in salt-sensitive individuals. Sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite participating in blood pressure regulation, has recently been identified as a novel lipid diuretic factor. However, the relationships among salt intake, circulating S1P levels, and blood pressure changes in human beings are unknown. Thus, we conducted this intervention trial to explore the effect of dietary salt intake on plasma S1P levels and to examine the relationship between S1P and blood pressure in Chinese adults.Methods: 42 participants (aged 18–65 years) were recruited from a rural community in Shaanxi, China. All participants first maintained their normal diet for 3 days, then sequentially ate a low-sodium diet (3.0 g/day NaCl) for 7 days, followed by a high-sodium diet (18.0 g/day NaCl) for 7 days. We assessed their plasma S1P concentrations on the last day of each intervention phase by liquid chromatography-tandem mass spectrometry. We classified the subjects who demonstrated at least a 10% increase in mean arterial pressure upon transitioning from a low-salt to a high-salt diet as salt-sensitive and the others as salt-resistant. Differences in repeated measures were analyzed by repeated-measures analysis of variance. Results: Plasma S1P levels decreased significantly from the baseline to low-salt diet period and increased from the low-salt to high-salt diet period. We observed this response in both salt-sensitive and salt-resistant individuals. Plasma S1P levels positively correlated with 24-hour urinary sodium excretion, but not 24-hour urinary potassium excretion. In line with plasma S1P level responses to salt intervention, systolic blood pressure (SBP) and mean arterial pressure (MAP) decreased from the baseline to low-salt diet period and increased from the low-salt to high-salt period. SBP positively correlated with plasma S1P and the correlation was stronger in salt-sensitive individuals than that in salt-resistant individuals. Conclusion: Low-salt dietary intervention decreases plasma S1P levels, whereas high-salt intervention reverses this change and S1P levels positively correlated with SBP in Chinese adults. This provides a high-efficiency and low-cost intervention for plasma S1P levels modulation, with implications for salt-induced blood pressure modulation. Trial registration: NCT02915315. Registered 27 September 2016, http://www.clinicaltrials.gov

High-salt diet upregulates kininogen and downregulates tissue kallikrein expression in Dahl-SS and SHR rats

1996 ◽  
Vol 271 (4) ◽  
pp. F824-F830 ◽  
Author(s):  
C. Wang ◽  
C. Chao ◽  
L. M. Chen ◽  
L. Chao ◽  
J. Chao
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Transcriptional Level ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Sd Rats

Tissue kallikrein cleaves low-molecular-weight (low-M(r)) kininogen to produce the vasoactive kinin peptide. It has been suggested that hypertensive patients with low urinary kallikrein excretion may have a defect in sodium handling. In this study, we examined the effect of a high-salt diet on the expression of tissue kallikrein and kininogen genes in Dahl salt-sensitive rats (Dahl-SS), spontaneously hypertensive rats (SHR), and normotensive Sprague-Dawley rats (SD) by Northern and Western blot analysis and radioimmunoassay. Control and experimental groups received normal and high-salt diets containing 0.4% and 8% NaCl, respectively, for 6 wk. High-salt diet induced a significant time-dependent increase of blood pressure in both strains of hypertensive rats and a slight but significant increase of blood pressure in normotensive SD rats. Hepatic kininogen mRNA levels of both Dahl-SS and SHR on a high-salt diet increased 2.4-fold and 2.0-fold, respectively, while alpha 1-antitrypsin mRNA levels were not changed in rats receiving high-salt diet. Immunoreactive total kininogen and low-M(r) kininogen (58 kDa) levels in sera increased in response to high-salt diet in both strains of hypertensive rats. In SD rats, the low-M(r) kininogen level in sera was unaltered, whereas total kininogen increased in response to high-salt diet. Tissue kallikrein mRNAs in the kidney and salivary glands of Dahl-SS, SHR, and SD rats were reduced, whereas beta-actin mRNA was not altered by high-salt diet. Similarly, immunoreactive intrarenal kallikrein levels were reduced in these rats in response to high-salt diet. These studies show that increases in blood pressure after salt loading in Dahl-SS and SHR are accompanied by increases in low-M(r) kininogen. Tissue kallikrein gene expression in hypertensive Dahl-SS and SHR and normotensive SD rats is suppressed after salt loading. These findings show that reduced renal kallikrein expression and increased kininogen expression is regulated at the transcriptional level during salt loading.

Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP

1996 ◽  
Vol 271 (1) ◽  
pp. R109-R114 ◽  
Author(s):  
S. W. John ◽  
A. T. Veress ◽  
U. Honrath ◽  
C. K. Chong ◽  
L. Peng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Volume ◽  
Volume Expansion ◽  
Salt Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Blood Volume Expansion ◽  
High Salt Intake ◽  
Low Salt

Atrial natriuretic peptide (ANP)-gene knockout mice of three genotypes (+/+, +/-, and -/-) were maintained on a low-salt diet (0.008% NaCl). They were then fed either the same low-salt diet or a high-salt diet (8% NaCl) for 1 wk. No differences were found among genotypes in daily food and water intakes or in urinary volume and electrolyte excretions. Arterial blood pressures measured in anesthetized animals at the end of the dietary regimen were significantly and similarly increased in -/- compared with +/+ mice on each diet. Renal excretion of fluid and electrolytes was measured in anesthetized mice before and after acute blood volume expansion. No genotype differences were observed before volume expansion. After volume expansion the wild-type (+/+) mice had much greater saluretic responses than either the heterozygous (+/-) or the homozygous mutant (-/-) animals on the low-salt diet but not on the high-salt diet. We conclude that ANP lowers blood pressure in the absence of detected changes in renal function; ANP is not essential for normal salt balance, even on high-salt intake; and ANP is essential for the natriuretic response to acute blood volume expansion on a low-salt but not high-salt intake.

scholarly journals Modulation of Plasma Sphingosine-1-Phosphate Levels via Dietary Salt Intervention in Chinese Adults:an Intervention Trial

2020 ◽  
Author(s):  
Qiong Ma ◽  
Chao Chu ◽  
Yan-bo Xue ◽  
Jia-wen Hu ◽  
Wen-ling Zheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Repeated Measures ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
Chinese Adults ◽  
Salt Diet ◽  
Low Salt ◽  
Sphingosine 1 Phosphate ◽  
Pressure Modulation

Abstract Background: Sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite, is involved in various pathophysiological processes,including blood pressure regulation. Salt is a crucial factor for blood pressure modulation,especially in salt-sensitive individuals who may develop earlier, more severe subclinical target organ damage than salt-resistant individuals.However, the relationships among salt intake, circulating S1P levels, and blood pressure changes are unknown. Thus, we conducted this intervention trial to explore the effect of dietary salt intake on plasma S1P levels and examine the relationship between S1P and blood pressure in Chinese adults.Methods:Forty-two participants (aged 18–65 years) were recruited from a rural community in Shaanxi, China. All participants first maintained their normal diet for 3 days, then sequentially ate a low-sodium diet (3.0 g/day NaCl) for 7 days, followed by a high-sodium diet (18.0 g/day NaCl) for 7 days. We assessed their plasma S1P concentrations on the last day of each intervention phase by liquid chromatography–tandem mass spectrometry. We classified the subjects who demonstrated at least a 10% increase in mean arterial pressure upon transitioning from a low-salt to a high-salt diet as salt-sensitive and the others as salt-resistant. Differences in repeated measures were analyzed by repeated-measures analysis of variance. Results:Plasma S1P levels decreased significantly from the baseline to low-salt diet period and increased from the low-salt tohigh-salt diet period. We observed this response in both salt-sensitive and salt-resistant individuals. Plasma S1P levels positively correlated with 24-hour urinary sodium excretion, but not 24-hour urinary potassium excretion. In line with plasma S1P level responses to salt intervention, systolic blood pressure and mean arterial pressure decreased from the baseline to low-salt diet period and increased from the low-salt to high-salt period.Systolic blood pressure positively correlated with plasma S1P; the correlation was stronger in salt-sensitive individuals than in salt-resistant individuals. Conclusion:Low-salt intervention decreased plasma S1P levels, whereas high-salt intervention reversed this changein Chinese adults. This finding provides evidence that salt moderation may be a high-efficiency, low-cost intervention for regulating circulating S1P levels, with implications for salt-induced blood pressure modulation. Trial registration: NCT02915315.Registered 27 September，2016,http://www.clinicaltrials.gov

scholarly journals Modulation of Plasma Sphingosine-1-Phosphate Levels via Dietary Salt Intervention in Chinese Adults:an Intervention Trial

2020 ◽  
Author(s):  
Qiong Ma ◽  
Chao Chu ◽  
Yan-bo Xue ◽  
Jia-wen Hu ◽  
Wen-ling Zheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Repeated Measures ◽  
Salt Intake ◽  
High Salt ◽  
Intervention Trial ◽  
Dietary Salt ◽  
Salt Diet ◽  
Low Salt ◽  
Sphingosine 1 Phosphate

Abstract Background Sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite, is involved in various pathophysiological processes,including blood pressure regulation. Salt is a crucial factor for blood pressure modulation,especially in salt-sensitive individuals who may develop earlier, more severe subclinical target organ damage than salt-resistant individuals.However, the relationships among salt intake, circulating S1P levels, and blood pressure changes are unknown. Thus, we conducted this intervention trial to explore the effect of dietary salt intake on plasma S1P levels and examine the relationship between S1P and blood pressure in Chinese adults.Methods Forty-two participants (aged 18–65 years) were recruited from a rural community in Shaanxi, China. All participants first maintained their normal diet for 3 days, then sequentially ate a low-sodium diet (3.0 g/day NaCl) for 7 days, followed by a high-sodium diet (18.0 g/day NaCl) for 7 days. We assessed their plasma S1P concentrations on the last day of each intervention phase by liquid chromatography–tandem mass spectrometry. We classified the subjects who demonstrated at least a 10% increase in mean arterial pressure upon transitioning from a low-salt to a high-salt diet as salt-sensitive and the others as salt-resistant. Differences in repeated measures were analyzed by repeated-measures analysis of variance.Results Plasma S1P levels decreased significantly from the baseline to low-salt diet period and increased from the low-salt tohigh-salt diet period. We observed this response in both salt-sensitive and salt-resistant individuals. Plasma S1P levels positively correlated with 24-hour urinary sodium excretion, but not 24-hour urinary potassium excretion. In line with plasma S1P level responses to salt intervention, systolic blood pressure and mean arterial pressure decreased from the baseline to low-salt diet period and increased from the low-salt to high-salt period.Systolic blood pressure positively correlated with plasma S1P; the correlation was stronger in salt-sensitive individuals than in salt-resistant individuals.Conclusion Low-salt intervention decreased plasma S1P levels, whereas high-salt intervention reversed this changein Chinese adults. This finding provides evidence that salt moderation may be a high-efficiency, low-cost intervention for regulating circulating S1P levels, with implications for salt-induced blood pressure modulation.Trial registration:NCT02915315.Registered 27 September,2016,http://www.clinicaltrials.gov

scholarly journals Cerebral Aβ40 and systemic hypertension

2017 ◽  
Vol 38 (11) ◽  
pp. 1993-2005 ◽  
Author(s):  
Hannah M Tayler ◽  
Jennifer C Palmer ◽  
Taya L Thomas ◽  
Patrick G Kehoe ◽  
Julian FR Paton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Arterial Pressure ◽  
High Salt ◽  
Systemic Hypertension ◽  
High Salt Diet ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
The Brain

Mid-life hypertension and cerebral hypoperfusion may be preclinical abnormalities in people who later develop Alzheimer’s disease. Although accumulation of amyloid-beta (Aβ) is characteristic of Alzheimer’s disease and is associated with upregulation of the vasoconstrictor peptide endothelin-1 within the brain, it is unclear how this affects systemic arterial pressure. We have investigated whether infusion of Aβ40 into ventricular cerebrospinal fluid modulates blood pressure in the Dahl salt-sensitive rat. The Dahl salt-sensitive rat develops hypertension if given a high-salt diet. Intracerebroventricular infusion of Aβ induced a progressive rise in blood pressure in rats with pre-existing hypertension produced by a high-salt diet ( p < 0.0001), but no change in blood pressure in normotensive rats. The elevation in arterial pressure in high-salt rats was associated with an increase in low frequency spectral density in systolic blood pressure, suggesting autonomic imbalance, and reduced cardiac baroreflex gain. Our results demonstrate the potential for intracerebral Aβ to exacerbate hypertension, through modulation of autonomic activity. Present findings raise the possibility that mid-life hypertension in people who subsequently develop Alzheimer’s disease may in some cases be a physiological response to reduced cerebral perfusion complicating the accumulation of Aβ within the brain.

Abstract MP70: Aldosterone And Inverse Salt Sensitivity Of Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Peng Xu ◽  
John J Gildea ◽  
Mahabuba Akhter ◽  
Robert M Carey ◽  
Wei Yue ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Sodium Reabsorption ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Low Salt ◽  
Harmful Effects

Salt sensitivity affects approximately 20% of adults worldwide and has similar mortality and morbidity sequalae as hypertension. Research has focused on the harmful effects of a high salt diet but have not focused on the harmful effects of a low salt diet. Inverse salt sensitive (ISS) individuals require high salt intake in order to maintain a normal blood pressure. Aldosterone increases ENaC and sodium reabsorption via the mineralocorticoid receptor (MR). We previously reported that αENaC was significantly lower in ISS renal tubule cells isolated from urine (uRTC), while these cells showed higher ENaC like activities under trypsin stimulation. We hypothesized that aldosterone may act as a stimulus and play a role in ISS high blood pressure on a low salt diet (LSD). Plasma aldosterone was significantly increased on LSD in all salt study participants, and ISS individuals showed the highest aldosterone level (ISS HS 3.8±0.38, n=26; ISS LS 35±3.38, n=22; SR HS 4.34±0.18, n=180; SR LS 32.62±1.6, n=152; SS HS 4.65±0.35, n=43; SS LS 26.08±2.18, n=38; HS Vs LS, p<0.001, two-way ANOVA). Moreover, both aldosterone and plasma renin activity (PRA) were significantly lower in salt sensitive (SS) individuals on LSD (PRA LS: ISS 6.05±0.87, n=17; SR 5.94±0.36, n=108; SS 4.43±0.57, n=34; p<0.05, one-way ANOVA), indicating LSD was protective to SS individuals. Treatment of uRTCs with 1 μM aldosterone increased MR and αENaC expression in ISS but not in SR (salt resistant) cells (MR: SR VEH 12164±213; SR Aldosterone 12327±128; ISS VEH 12128±40 vs ISS Aldosterone 13506±128, n=3, p<0.001, two-way ANOVA; αENaC: SR VEH 5023±46; SR Aldosterone 4895±55; ISS VEH 4270±21 vs ISS Aldosterone 5013±113, n=3, p<0.001, two-way ANOVA). High salt treatment further decreased MR in ISS but not in SR cells (ISS: 142mM 11066±188 vs 192mM 10425±74; p<0.05, n=3 two-way ANOVA). These results are consistent with the hypothesis that ISS individuals retain excess Na + and exhibit decreased BP when compared to SR or SS individuals under high salt diet, but reabsorb more sodium and exhibit elevated blood pressure under low salt diet. Higher circulating aldosterone and ex-vivo urine derived renal cell aldosterone sensitivity under low salt conditions may be a novel diagnostic test to identify ISS individuals.

Evidence for endothelin involvement in the response to high salt

2001 ◽  
Vol 281 (1) ◽  
pp. F144-F150 ◽  
Author(s):  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Receptor Activation ◽  
Blood Pressure Regulation ◽  
High Salt ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Low Salt

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ETB receptor, may participate in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment ( n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 ± 2 mmHg) compared with rats on the low-salt diet (103 ± 2 mmHg; P < 0.05). All rats were then treated with the ETB receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg · kg−1 · day−1. ETB blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 ± 3 vs. 115 ± 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ETA receptor activation, all rats were then given the ETA-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ETB blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 ± 3 mmHg) or low-salt (101 ± 3 mmHg) diet. These results support the hypothesis that endothelin, through the ETB receptor, participates in blood pressure regulation in the response to salt loading.

scholarly journals Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase

2012 ◽  
Vol 13 (3) ◽  
pp. 353-359 ◽  
Author(s):  
MA Bayorh ◽  
A Rollins-Hairston ◽  
J Adiyiah ◽  
D Lyn ◽  
D Eatman
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Prostaglandin E ◽  
Renal Tubules ◽  
Protective Effects ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Low Salt ◽  
Cox 2

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E2 (PGE2). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE2. The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.

Abstract 495: A Novel Test for Low Salt Sensitivity: Angiotensin type-II Receptor Recruitment After Dopamine-1 Receptor Stimulation in Urine-Derived Renal Proximal Tubule Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
John J Gildea ◽  
Staci A Keene ◽  
Dylan T Lahiff ◽  
Robert E Van Sciver ◽  
Cynthia D Schoeffel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Flow Cytometry ◽  
Clinical Study ◽  
Salt Sensitivity ◽  
High Salt ◽  
Salt Diet ◽  
Independent Events ◽  
Angiotensin Type 2 Receptor ◽  
Low Salt ◽  
Angiotensin Type

Salt-sensitivity of blood pressure is an inappropriate increase in blood pressure following high salt intake. Subjects in our clinical study were typed according to their salt-sensitivity status into 3 categories: High-Salt-Sensitive (HSS; ≥ 7 mmHg increase in mean arterial pressure (MAP) on a high salt diet of 300 mEq of sodium, 17% prevalence), Low-Salt-Sensitive (LSS:, who paradoxically showed a ≥ 7 mmHg increase in MAP on a low salt diet of 10 mEq of sodium, 11% prevalence), and Salt-Resistant (SR, individuals who showed no significant increase in blood pressure on either diet, 72% prevalence). We previously demonstrated that LSS subjects show increased recruitment of the natriuretic dopamine-1 receptor (D1R) to the plasma membrane following a salt stimulation as compared to HSS subjects. Stimulation of the D1R in RPTC with fenoldopam (dopaminergic agonist) results in recruitment of the natriuretic angiotensin type-2 receptor (AT2R) to the cell surface. We hypothesized that LSS individuals may also demonstrate an enhanced AT2R RPTC membrane recruitment compared to HSS individuals when challenged with fenoldopam. In order to gain access to fresh RPTC from each subject, we isolated exfoliated RPTC from randomly voided urine from SR, LSS, and HSS subjects from our clinical study. We measured three subjects from each category with a minimum of three voids for each subject. We counted individual cells as independent events using both the confocal microscope (n=245) and the flow cytometer (n=5344). We found an inverse correlation between AT2R recruitment and the degree of salt-sensitivity of blood pressure. Fenoldopam stimulated AT2R recruitment as measured by confocal microscopy (y = -0.0047x + 0.4966, R2 = 0.2488, P<0.0001) and flow cytometry (y =-0.057x + 1.5645, R2=0.2912, P=0.0185). Flow cytometry provided a more sensitive diagnostic for LSS than HSS subjects. AT2R recruitment was more predictive of LSS than HSS. AT2R recruitment may be used as a rapid method to test for LSS individuals who need to be identified and encouraged to increase their sodium intake in order to avoid paradoxical hypertension.

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