Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects

1998 ◽  
Vol 95 (2) ◽  
pp. 157-164 ◽  
Author(s):  
M. FOO ◽  
A. E. DENVER ◽  
S. W. COPPACK ◽  
J. S. YUDKIN
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Geometric Mean ◽  
High Salt ◽  
High Dose ◽  
Metabolic Clearance ◽  
Salt Loading ◽  
Leg Blood Flow ◽  
Low Salt

1.The aim of this study was to determine the effects of high (220 ;mmol/day) and low (40 ;mmol/day) salt intake for 6 days on blood pressure, leg blood flow and insulin sensitivity in 18 ;healthy normotensive subjects. 2.Twenty-four-hour ambulatory blood pressure was measured at baseline, during salt-loading and salt-depletion. Insulin sensitivity was determined by a two-step euglycaemic–hyperinsulinaemic clamp (low and high insulin infusion rates: 40 and 600 ;m-unit·min-1·m-2 respectively) and leg blood flow by plethysmography. 3.Salt-loading resulted in changes in weight [change between salt-loading and salt-restriction: δ =+0.45 (S.D.±0.69) ;kg, P = 0.015], plasma renin [δ =-11.5 (S.D.±12.9) ;μ-units/l, P = 0.001] and urinary noradrenaline [δ =-8.6 (S.D.±18.7) ;nmol/mmol creatinine, P = 0.05]. There were borderline significant increases in 24-h systolic blood pressure [δ =+5.8 (S.D.±14.2) mmHg, P = 0.06] and plasma volume [δ =+0.29 (S.D.±0.67) litres, P = 0.08]. 4.Insulin sensitivity was similar in both salt states. Geometric mean metabolic clearance rate of low-dose insulin: low salt, 5.13 (S.D.×/÷1.35) dl/min; high salt, 4.94 (S.D.×/÷1.37) dl/min, P = 1.0. Geometric mean metabolic clearance rate of high-dose insulin: low salt, 9.68 ;dl/min (S.D.×/÷1.30); high salt, 9.68 (S.D.×/÷1.27) dl/min, P = 0.69. 5.Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt. Percentage change of blood flow on low salt, δ =+36.6 (S.D.±22.9)% versus high salt, δ =+66.8 (S.D.±52.2)%, P = 0.03. 6.There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate. 7.We conclude that salt-loading, despite changing body weight, the renin–angiotensin–aldosterone system, urinary noradrenaline and the leg blood flow response to insulin, has no significant effect on insulin sensitivity. Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal.

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.

Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects

1998 ◽  
Vol 95 (2) ◽  
pp. 157 ◽  
Author(s):  
M. FOO ◽  
A.E. DENVER ◽  
S.W. COPPACK ◽  
J.S. YUDKIN
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Normal Subjects ◽  
Limb Blood Flow ◽  
Salt Loading

Dependence of Renal Vasodilator Effect of Captopril on Prevailing Plasma Renin Level in the Dog: Influence of DOCA–Salt Treatment

1982 ◽  
Vol 63 (4) ◽  
pp. 355-360 ◽  
Author(s):  
P. C. Wong ◽  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Plasma Renin Activity ◽  
Renal Blood Flow ◽  
Plasma Renin ◽  
High Salt ◽  
Renin Activity ◽  
Arterial Blood ◽  
Low Salt ◽  
Renin Level

1. The blood pressure and renal blood flow response to captopril (0·2 mg/kg, intravenously) was studied in low salt, normal, and high salt fed conscious dogs, and in a group of DOCA-salt treated dogs. 2. Mean arterial blood pressure was decreased and renal blood flow increased most in the low salt group, but significant changes were also obtained in the normal group. The high salt and DOCA-salt groups were only marginally affected by captopril. 3. When the data from all four groups of dogs were subjected to regression analysis, there was a significant relationship (r = 0·68) between the prevailing plasma renin activity and the increase in renal blood flow caused by captopril. 4. The results suggest that renal vasodilatation resulting from converting enzyme inhibition is mainly due to a decrease in the level of circulating angiotensin II, and that even in the normal conscious dog the prevailing plasma renin activity can affect blood pressure and renal blood flow.

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.

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.

Abstract 15630: Direct Renin Inhibition With Aliskiren Improves Ischemia-Induced Neovascularization

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Michel Desjarlais ◽  
Sylvie Dussault ◽  
Wahiba Dhahri ◽  
Alain Rivard
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renin Angiotensin System ◽  
Cellular Migration ◽  
High Dose ◽  
Hindlimb Ischemia ◽  
Adhesive Properties ◽  
Tubule Formation ◽  
Renin Inhibition

Background: The activation of the renin-angiotensin system is associated with impaired formation of new blood vessels (neovascularization) in response to ischemia. Aliskiren is the only direct renin inhibitor that is clinically used as an orally active antihypertensive drug. Here we tested the hypothesis that aliskiren might improve neovascularization following ischemia. Methods and Results: C57BL/6 mice were treated with a high dose of aliskiren (50 mg/kg), a low dose of aliskiren (10 mg/kg), or drinking water only. After two weeks of treatment, hindlimb ischemia was surgically induced by femoral artery removal. Treatment with aliskiren led to a significantly faster rate of blood flow recovery after hindlimb ischemia (Laser Doppler). Interestingly the lower dose of aliskiren, which did not reduce blood pressure, provided similar improvement of blood flow recuperation compared to the higher dose of aliskiren. At day 21 after surgery, Doppler flow ratios were significantly improved in mice treated with aliskiren (0.69+/-0.07 vs. 0.52+/-0.03; p<0.05). This was associated with an increased expression of angiogenic factors in ischemic muscles, including VEGF and eNOS. Endothelial progenitor cells (EPCs) have been shown to have an important role in postnatal neovascularisation. We found that aliskiren significantly increased the number of bone marrow EPCs at day 7 after ischemia (172+/-7% increase; p<0.05). Moreover, the adhesive properties of EPCs were significantly improved in mice treated with aliskiren (175+/-5% increase; p<0.05). In vitro, aliskiren improves cellular migration and tubule formation in HUVECs. This is associated with an increased expression of nitric oxide (DAF staining), and a significant reduction of oxidative stress levels (DHE staining). Importantly, the antioxidant and angiogenic properties of aliskiren in HUVECs are abolished following treatment with the NOS inhibitor L-NAME. Conclusions: Direct renin inhibition with aliskiren leads to improved ischemia-induced neovascularization that is not dependant on blood pressure lowering. The mechanisms involve beneficial effects of aliskiren on NO and angiogenic pathways in ischemic tissues, together with an increase in the number and the functional activity of EPCs.

Salt intake and insulin sensitivity in healthy human volunteers

2007 ◽  
Vol 113 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Raymond R. Townsend ◽  
Shiv Kapoor ◽  
Christopher B. McFadden
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Infusion ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Euglycaemic Clamp ◽  
Noradrenaline Concentration ◽  
Low Salt

The literature on salt intake and insulin sensitivity presents a mixed picture, as some studies have shown an increase, whereas others have shown a decrease, in insulin action as sodium intake is enhanced. In some cases, this may relate to the study of salt intake in patients with co-morbidities such as hypertension or diabetes. In the present study, we selected healthy normotensive lean volunteers who underwent a euglycaemic clamp following 6 days of a low-salt diet (20 mmol sodium daily) and, subsequently, 6 days of a high-salt diet (200 mmol sodium daily). Our results show an increase in insulin-mediated glucose disposal during euglycaemic clamp conditions that was significantly higher following the high-salt diet compared with the low-salt diet (7.41±0.41 compared with 6.11±0.40 mg·kg−1 of body weight·min−1 respectively; P=0.03). We measured calf blood flow before and during insulin infusion (no significant change after the two dietary salt interventions was detected) and plasma non-esterified fatty acids (also no significant differences were detected). We observed the expected increases in renin concentration and aldosterone activity in subjects on the low-salt diet, and also observed a significantly less increase in plasma noradrenaline concentration during euglycaemic insulin infusion following the high-salt compared with the low-salt diet. We propose that the 4–5-fold increase in serum aldosterone and the greater increase in plasma noradrenaline concentration following the low-salt intervention compared with the high-salt period may have contributed to the differences in insulin sensitivity following the adjustment in dietary sodium intake.

scholarly journals Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity

2003 ◽  
Vol 88 (9) ◽  
pp. 4180-4185 ◽  
Author(s):  
Michiel N. Kerstens ◽  
Frank G. H. van der Kleij ◽  
Arnold H. Boonstra ◽  
Wim J. Sluiter ◽  
Jan Koerts ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Vascular Resistance ◽  
High Salt ◽  
Percentage Change ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Cortisol Metabolism ◽  
Normotensive Subjects ◽  
Renal Vascular

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (∑metabolites) increased in sr subjects (3.8 ± 1.6 vs. 3.1 ± 1.1 μg/min per square meter, P &lt; 0.05) and decreased in ss subjects (2.3 ± 1.0 vs. 2.9 ± 1.1 μg/min per square meter, P &lt; 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in ∑metabolites (P &lt; 0.05) and positively with the percentage change in renal vascular resistance (P &lt; 0.05). ∑metabolites during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P &lt; 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in ∑metabolites (P &lt; 0.01). Parameters of 11β-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.

scholarly journals Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

2021 ◽  
Vol 7 ◽  
Author(s):  
Knut Asbjørn Rise Langlo ◽  
Gustavo Jose Justo Silva ◽  
Tina Syvertsen Overrein ◽  
Volker Adams ◽  
Ulrik Wisløff ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Ejection Fraction ◽  
Thrombotic Microangiopathy ◽  
Hypertensive Encephalopathy ◽  
High Salt ◽  
Preserved Ejection Fraction ◽  
Circulating Micrornas ◽  
Low Salt

There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p &lt; 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75–0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved.

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