Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

2005 ◽  
Vol 289 (4) ◽  
pp. R1099-R1106 ◽  
Author(s):  
Amanda C. Boyce ◽  
Karen J. Gibson ◽  
E. Marelyn Wintour ◽  
Irene Koukoulas ◽  
Eugenie R. Lumbers
Keyword(s):  
Amino Acid ◽  
Renin Angiotensin System ◽  
Sodium Reabsorption ◽  
Mrna Levels ◽  
Renal Growth ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Glomerulotubular Balance

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 ± 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses ( P < 0.05), and renal angiotensinogen mRNA levels were ∼2.6-fold higher ( P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed ( P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were ∼two-fold higher throughout infusion ( P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 ± 6.5 to 53.7 ± 10.2%), did not return to control levels (36.1 ± 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 ± 25 to 261 ± 75 μmol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.

scholarly journals Prolonged amino acid infusion into intrauterine growth-restricted fetal sheep increases leucine oxidation rates

2018 ◽  
Vol 315 (6) ◽  
pp. E1143-E1153 ◽  
Author(s):  
Sandra G. Wai ◽  
Paul J. Rozance ◽  
Stephanie R. Wesolowski ◽  
William W. Hay ◽  
Laura D. Brown
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Intrauterine Growth ◽  
Leucine Oxidation ◽  
Fetal Plasma ◽  
Oxidation Rates

Overcoming impaired growth in an intrauterine growth-restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We subjected fetal sheep to chronic placental insufficiency and tested whether prolonged amino acid infusion would increase protein accretion in these IUGR fetuses. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg−1·day−1 (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in the IUGR-AA than IUGR-Sal group ( P < 0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were fourfold higher in the IUGR-AA group ( P < 0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus the total amino acid delivery rate (net umbilical amino acid uptake + infusion rate) was higher in the IUGR-AA than IUGR-Sal group (30 ± 4 vs. 19 ± 1 μmol·kg−1·min−1, P < 0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate, measured using a leucine tracer, was higher in the IUGR-AA than IUGR-Sal group (2.5 ± 0.3 vs. 1.7 ± 0.3 μmol·kg−1·min−1, P < 0.05). Fetal protein accretion rate was not statistically different between the IUGR groups (1.6 ± 0.4 and 0.8 ± 0.3 μmol·kg−1·min−1 in IUGR-AA and IUGR-Sal, respectively) due to variability in response to amino acids. Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.

Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep

2001 ◽  
Vol 280 (4) ◽  
pp. R1045-R1051 ◽  
Author(s):  
Eugenie R. Lumbers ◽  
Alistair J. Gunn ◽  
David Y. Zhang ◽  
June J. Wu ◽  
Linda Maxwell ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Hydrops Fetalis ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Tissue Edema ◽  
Nonimmune Hydrops ◽  
Sheep Fetus

This study examined the hypothesis that the development of hydrops fetalis after asphyxia in the 0.6 gestation sheep fetus would be associated with activation of the fetal renin-angiotensin system (RAS). Fetuses were randomly assigned to either sham occlusion ( n = 7) or to 30 min of asphyxia induced by complete umbilical cord occlusion for 30 min ( n = 8). Asphyxia led to severe bradycardia and hypotension that resolved after release of occlusion. After occlusion, plasma renin concentration was significantly increased in the asphyxia group compared with controls ( P < 0.005) after 3 min (16.3 ± 5.3 vs. 4.1 ± 1.3 ng · ml−1 · h−1), and 72 h (30.6 ± 6.3 vs. 3.7 ± 1.2 ng · ml−1 · h−1). Renal renin concentrations and mRNA levels were significantly greater in the asphyxia group after 72 h of recovery. All fetuses in the asphyxia group showed generalized tissue edema, ascites, and pleural effusions after 72 h of recovery. In conclusion, asphyxia in the preterm fetus caused sustained activation of the RAS, which was associated with hydrops fetalis.

Maternal renal insufficiency alters plasma composition and renal function in the fetal sheep

2007 ◽  
Vol 292 (3) ◽  
pp. R1204-R1211 ◽  
Author(s):  
Karen J. Gibson ◽  
Amanda C. Boyce ◽  
Bilal M. Karime ◽  
Eugenie R. Lumbers
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Adult Life ◽  
Sodium Reabsorption ◽  
Width Ratio ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Plasma Chloride ◽  
Distal Delivery

To determine the effects of chronic maternal renal insufficiency on fetal renal function, we studied nine fetuses whose mothers underwent subtotal nephrectomy at least 2 mo before mating (STNxF) and seven fetuses from intact ewes (IntF) (126–128 days of gestation, term 150 days). STNxF had lower hematocrit ( P < 0.05), plasma chloride ( P < 0.01), and creatinine levels ( P < 0.01), and the length-to-width ratio of their kidneys was reduced ( P < 0.05). They excreted twice as much urine ( P < 0.05) and sodium ( P < 0.01). Total ( P = 0.01) and proximal fractional sodium reabsorptions ( P < 0.05) were lower in STNxF; distal delivery of sodium ( P < 0.05) and distal fractional sodium reabsorption ( P < 0.05) were higher. They tended to have suppressed renin levels ( P = 0.06). Infusions of amino acids (alanine, glycine, proline, and serine at 0.32 mmol/min for 1 h and 0.64 mmol/min for 2 h intravenously), known to stimulate renal blood flow and glomerular filtration rate in fetal sheep, did so in IntF ( P < 0.01). Arterial pressure also increased ( P < 0.01). These effects were not observed in STNxF. In summary, chronic maternal renal insufficiency was associated with profound alterations in fetal renal excretion of fluid and electrolytes and impaired renal hemodynamic and glomerular responses to amino acid infusion. Whether these marked changes in the renal function of fetuses carried by STNx ewes are associated with alterations in renal function in postnatal or adult life remains to be determined.

Renal responses to amino acids in the sheep fetus

1996 ◽  
Vol 270 (6) ◽  
pp. R1226-R1230 ◽  
Author(s):  
L. L. Woods ◽  
A. R. Hohimer ◽  
L. E. Davis
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Intake ◽  
Amino Nitrogen ◽  
Maternal Plasma ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Nitrogen Levels ◽  
Amino Acid Levels

Adult animals and humans are known to increase renal blood flow and glomerular filtration rate (GFR) in response to an acute protein load or amino acid infusion; however, the ontogeny of this phenomenon is not known. This study was designed to test the hypothesis that, despite normally high baseline amino acid levels in the fetus, increases in plasma amino acids stimulate increases in GFR before birth. Eight chronically instrumented fetal sheep (126 +/- 1 days gestation) were infused with a mixture of amino acids (0.15 and 0.30 mmol . kg-1 . min-1 i.v.). Plasma alpha-amino nitrogen levels increased significantly from 7.1 +/- 0.3 to 13.0 +/- 0.9 and 25.5 +/- 2.1 mg/dl, respectively, in response to the two doses, and GFR increased significantly from 3.2 +/- 0.4 to 4.0 +/- 0.5 and 4.6 +/- 0.5 ml/min, respectively. Arterial pressure did not change. Renal amino acid reabsorption was significantly increased at all time points during the amino acid infusion, reaching a value nearly five times that of control by the last clearance period. Na+ reabsorption was also increased throughout the infusion. Na+, K+, and Cl- excretions increased significantly only at the very last time point. These data indicate that the mechanism or mechanisms responsible for amino acid-induced hyperfiltration are present and functional even before birth in the sheep. Because maternal eating patterns and protein intake are known to change maternal plasma amino acid levels and amino acids are actively transported across the placenta, our findings suggest that both acute and chronic changes in maternal protein intake may alter fetal renal function.

The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep

2007 ◽  
Vol 85 (6) ◽  
pp. 597-605 ◽  
Author(s):  
Amanda C. Boyce ◽  
Karen J. Gibson ◽  
E. Marelyn Wintour ◽  
Irene Koukoulas ◽  
Kathryn L. Gatford ◽  
...  
Keyword(s):  
Renal Function ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Insulin Levels ◽  
Igf I

We imposed a sustained reduction in glucose supply to late-gestation fetal sheep to see whether the reduction in glucose and insulin levels affected renal growth, renin expression and synthesis, and renal function. Maternal glucose concentrations were lowered to 1.7–1.9 mmol/L for 12–13 days by i.v. insulin infusion (n = 9, 121 days gestation, term = 150 days). Control ewes (n = 7) received vehicle. Maternal and fetal glucose concentrations were 40% and 31% lower than in controls (p < 0.001), respectively. Fetal plasma insulin levels fell 36% ± 7% by day 7 (p < 0.05); IGF-I levels were unchanged. Arterial PO2 and pH increased and PCO2 fell (p < 0.05). Renal function was largely unaffected. Longitudinal growth was 28% slower and spleen weights were 36% smaller (p < 0.05); body and kidney weights were not affected. Renal renin levels and renin, angiotensinogen, and angiotensin receptor mRNA levels were similar to those of controls. Plasma renin levels increased from 2.1 ± 0.6 to 7.6 ± 2.8 ng angiotensin I·mL–1·h–1 (p = 0.01). Thus reductions in fetal glucose and insulin levels in late gestation that were sufficient to retard skeletal growth had no effect on kidney growth or function or the renal renin–angiotensin system, possibly because IGF-I levels were not reduced. There was, however, increased activity of the circulating renin–angiotensin system similar to that seen during insulin-induced hypoglycaemia.

Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects

Diabetes ◽  
1989 ◽  
Vol 38 (1) ◽  
pp. 75-83 ◽  
Author(s):  
R. Nosadini ◽  
R. Trevisan ◽  
P. Fioretto ◽  
A. Semplicini ◽  
B. Sama ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ketone Body ◽  
Acid Infusion ◽  
Amino Acid Infusion

scholarly journals Effect of Insulin with Concurrent Amino Acid Infusion on Protein Metabolism in Rapidly Growing Pubertal Children with Type 1 Diabetes

2005 ◽  
Vol 58 (2) ◽  
pp. 229-234 ◽  
Author(s):  
Mushtaq A Godil ◽  
Thomas A Wilson ◽  
Peter J Garlick ◽  
Margaret A McNurlan
Keyword(s):  
Type 1 Diabetes ◽  
Amino Acid ◽  
Protein Metabolism ◽  
Acid Infusion ◽  
Amino Acid Infusion

scholarly journals A novel role for miR-133a in centrally mediated activation of the renin-angiotensin system in congestive heart failure

2017 ◽  
Vol 312 (5) ◽  
pp. H968-H979 ◽  
Author(s):  
Neeru M. Sharma ◽  
Shyam S. Nandi ◽  
Hong Zheng ◽  
Paras K. Mishra ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

An activated renin-angiotensin system (RAS) within the central nervous system has been implicated in sympathoexcitation during various disease conditions including congestive heart failure (CHF). In particular, activation of the RAS in the paraventricular nucleus (PVN) of the hypothalamus has been recognized to augment sympathoexcitation in CHF. We observed a 2.6-fold increase in angiotensinogen (AGT) in the PVN of CHF. To elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of the 3′-untranslated region (3′-UTR) of AGT and found a potential binding site for microRNA (miR)-133a. We hypothesized that decreased miR-133a might contribute to increased AGT in the PVN of CHF rats. Overexpression of miR-133a in NG108 cells resulted in 1.4- and 1.5-fold decreases in AGT and angiotensin type II (ANG II) type 1 receptor (AT1R) mRNA levels, respectively. A luciferase reporter assay performed on NG108 cells confirmed miR-133a binding to the 3′-UTR of AGT. Consistent with these in vitro data, we observed a 1.9-fold decrease in miR-133a expression with a concomitant increase in AGT and AT1R expression within the PVN of CHF rats. Furthermore, restoring the levels of miR-133a within the PVN of CHF rats with viral transduction resulted in a significant reduction of AGT (1.4-fold) and AT1R (1.5-fold) levels with a concomitant decrease in basal renal sympathetic nerve activity (RSNA). Restoration of miR-133a also abrogated the enhanced RSNA responses to microinjected ANG II within the PVN of CHF rats. These results reveal a novel and potentially unique role for miR-133a in the regulation of ANG II within the PVN of CHF rats, which may potentially contribute to the commonly observed sympathoexcitation in CHF. NEW & NOTEWORTHY Angiotensinogen (AGT) expression is upregulated in the paraventricular nucleus of the hypothalamus through posttranscriptional mechanism interceded by microRNA-133a in heart failure. Understanding the mechanism of increased expression of AGT in pathological conditions leading to increased sympathoexcitation may provide the basis for the possible development of new therapeutic agents with enhanced specificity.

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