Circulating Angiotensin II and Renal Sodium Handling in Man: A Dose-Response Study

1993 ◽  
Vol 85 (2) ◽  
pp. 147-156 ◽  
Author(s):  
A. R. A. Rahman ◽  
J. G. Motwani ◽  
C. C. Lang ◽  
A. D. Struthers
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Sodium Excretion ◽  
Response Curve ◽  
Statistical Significance ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Dose Response Curve ◽  
Sodium Reabsorption ◽  
Flat Dose

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min−1 kg−1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: + 3.4 ±1.77, −1.26 ±0.49 (P <0.05), −2.75±1.23 (P <0.05), −4.21 ± 0.82 (P <0.05) and −6.51 ±1.07 (P <0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min−1 kg−1. The urinary sodium excretion, in μmol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 ±21.2, −18.9± 29.6, −37.0±11.6 (P <0.05), −67.7 ± 19.6 (P <0.01) and −63.8±14.3 (P <0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min−1 kg−1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.

scholarly journals Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion

2015 ◽  
Vol 26 (12) ◽  
pp. 2953-2962 ◽  
Author(s):  
Matthew A. Sparks ◽  
Johannes Stegbauer ◽  
Daian Chen ◽  
Jose A. Gomez ◽  
Robert C. Griffiths ◽  
...  
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Angiotensin Ii Receptors ◽  
Vascular Type

Mechanisms of angiotensin II natriuresis and antinatriuresis

1985 ◽  
Vol 249 (2) ◽  
pp. F299-F307 ◽  
Author(s):  
M. E. Olsen ◽  
J. E. Hall ◽  
J. P. Montani ◽  
A. C. Guyton ◽  
H. G. Langford ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Distal Tubule ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Anesthetized Dogs

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR

2011 ◽  
Vol 12 (4) ◽  
pp. 394-403 ◽  
Author(s):  
Silmara Ciampone ◽  
Rafael Borges ◽  
Ize P de Lima ◽  
Flávia F Mesquita ◽  
Elizabeth C Cambiucci ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Exercise Training ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Receptor Expression ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin–angiotensin–aldosterone (RAS) intracellular pathways in conscious, trained Okamoto–Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHRT) rats, compared with sedentary SHR (SHRS), despite a significantly decreased creatinine clearance (CCr). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1R in the entire kidney of TSHR rats, compared with SSHR. Conversely, the expression of the AT2R, in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in TSHR rats compared with age-matched SSHR rats.

Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade

1994 ◽  
Vol 266 (1) ◽  
pp. F117-F119 ◽  
Author(s):  
J. A. Haas ◽  
J. C. Lockhart ◽  
T. S. Larson ◽  
T. Henrikson ◽  
F. G. Knox
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Treated Group ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Angiotensin System ◽  
Before And After

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

The Influence of Sodium Intake on the Pressor Response to Angiotensin II in the Unanaesthetized Rat

1976 ◽  
Vol 50 (4) ◽  
pp. 285-291
Author(s):  
Barbara L. Slack ◽  
J. M. Ledingham
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Response Curves ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
High Sodium Diet

1. Dose—response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2·5% (w/w) or 0·007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose—response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose—response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose—response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose—response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin—angiotensin system, on the rate of in-activation of angiotensin and on a change in initial length of the muscle fibre.

The control of sodium excretion

1978 ◽  
Vol 235 (3) ◽  
pp. F163-F173 ◽  
Author(s):  
H. E. de Wardener
Keyword(s):  
Proximal Tubule ◽  
Sodium Excretion ◽  
Collecting Duct ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Loop Of Henle ◽  
Salt Loading ◽  
Large Fluctuations

The kidneys of a normal man filter approximately 24,000 meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq change in 24-h urinary sodium excretion. The control of urinary sodium excretion, therefore, depends, first, on ensuring that the bulk of the sodium is reabsorbed, a function which is carried out in the proximal tubule and ascending loop of Henle. Second, it depends on adjusting the reabsorption of the small quantity of sodium which is delivered into the collecting duct so that the amount excreted in the urine is that required to maintain sodium balance. The bulk reabsorptive mechanisms can be considered as buffers to prevent large fluctuations in the amount of sodium delivered to the collecting duct, thus facilitating the fine adjustments of reabsorption which are made at this site. In conditions other than extreme salt loading or deprivation, changes in sodium reabsorption in the proximal tubule and loop of Henle probably have little, if any, effect on urinary sodium excretion. Sodium reabsorption in the proximal tubule and the collecting duct appears to be influenced by unidentified circulating substances.

Verapamil prevents insulin antinatriuresis in euglycemic rats

1992 ◽  
Vol 262 (6) ◽  
pp. R1145-R1148 ◽  
Author(s):  
A. K. Gupta ◽  
R. Clark ◽  
K. A. Kirchner
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Calcium Entry ◽  
Urinary Sodium ◽  
Inulin Clearance ◽  
Insulin Administration ◽  
Lower Baseline

To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.

scholarly journals Effect of dose and duration of reduction in dietary sodium on blood pressure levels: systematic review and meta-analysis of randomised trials

BMJ ◽  
2020 ◽  
pp. m315 ◽  
Author(s):  
Liping Huang ◽  
Kathy Trieu ◽  
Sohei Yoshimura ◽  
Bruce Neal ◽  
Mark Woodward ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Dose Response ◽  
Sodium Excretion ◽  
Meta Analysis ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Dietary Sodium ◽  
Sodium Reduction ◽  
Randomised Trials

AbstractObjectiveTo examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration.DesignSystematic review and meta-analysis following PRISMA guidelines.Data sourcesOvid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019.Inclusion criteriaRandomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion.Data extraction and analysisTwo of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression.Results133 studies with 12 197 participants were included. The mean reductions (reduced sodium v usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days’ duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction.ConclusionsThe magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure.Systematic review registrationPROSPERO CRD42019140812.

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