Renal function and angiotensin AT1 receptor expression in young rats following intrauterine exposure to a maternal low-protein diet

2003 ◽  
Vol 104 (6) ◽  
pp. 607-614 ◽  
Author(s):  
Vandana SAHAJPAL ◽  
Nick ASHTON
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Filtration Rate ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Kidney Weight ◽  
Low Protein

Recent studies have proposed a link between impaired nephrogenesis, decreased activity of the renin–angiotensin system and the onset of hypertension in rats exposed in the uterus to a maternal low-protein diet. However, there is no detailed information about renal function in this model; hence the aim of the present study was to assess renal function in young (4-week-old) rats exposed in the uterus to a maternal low-protein diet. Pregnant Wistar rats were fed isocalorific diets containing either 18% (normal protein; offspring denoted NP rats) or 9% (low protein; offspring denoted LP rats) (w/w) protein from conception until birth. At 4 weeks of age, male offspring were anaesthetized and prepared for the study of renal function, during which animals received saline alone, a bolus of enalapril (5 mg·kg-1) or a bolus of enalapril followed by an infusion of angiotensin II (30 ng·min-1·kg-1). Under control conditions, renal haemodynamic and tubular function did not differ. However, when challenged with angiotensin II, LP rats responded with a greater decrease in glomerular filtration rate than did NP rats [NP, 2.0±0.2 ml·min-1·g-1 kidney weight (n=9); LP, 1.0±0.2 ml·min-1·g-1 kidney weight (n=5); P<0.05]. Renal electrolyte excretion did not differ. LP rats had significantly fewer glomeruli than NP rats (P<0.01). Renal angiotensin II AT1 receptor expression was increased (P<0.01) by 24% in LP rats. It is concluded that blood pressure may be elevated in LP rats in order to maintain glomerular filtration rate against a background of fewer nephrons. Increased AT1 receptor expression, which may arise as a result of the direct effect of protein restriction or in response to the reported decrease in renal tissue angiotensin II concentration, could also contribute to the elevated blood pressure of this model.

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat

2000 ◽  
Vol 98 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Rachel C. SHERMAN ◽  
Simon C. LANGLEY-EVANS
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Control Diet ◽  
In Utero ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Human Populations ◽  
Postnatal Life ◽  
Blood Pressure Elevation ◽  
Low Protein

Epidemiological evidence from diverse human populations, supported by experimental evidence from animal models, suggests that maternal nutrition during pregnancy is an important fetal programming influence upon cardiovascular disease. Experiments with a low-protein-diet model of rat pregnancy suggest a role for the renin–angiotensin system in the programming mechanism, since fetal undernutrition permanently elevates pulmonary and plasma angiotensin-converting enzyme activity. Long-term beneficial effects of captopril on blood pressure in this model require further investigation in order to clarify the role of angiotensin II. Pregnant rats were fed a control diet containing 18% (w/w) casein as the protein source or a low-protein diet containing 9% (w/w) casein. Between the ages of 2 and 4 weeks postnatally, mothers and their pups were treated with losartan or nifedipine. All pups in the study had blood pressure determined at 4 and 12 weeks of age using a tail cuff. Animals exposed to the low-protein diet in utero and not subjected to drug treatment had elevated blood pressure relative to control rats (mean increase of 27 mmHg; P < 0.001). Treatment of rats exposed to the control diet in utero with either nifedipine or losartan between 2 and 4 weeks of age did not alter their blood pressure. Nifedipine had no effect upon the blood pressure of low-protein-exposed pups, but losartan prevented the blood pressure elevation in these animals. Between 4 and 12 weeks of age, blood pressure increased significantly in all groups (P < 0.001). The pattern of blood pressure among the groups was identical to that observed at 4 weeks, suggesting that the observed early effects of losartan would be maintained into adult life. The data are consistent with the hypothesis that angiotensin II plays a major role in the prenatal programming of hypertension. The action of angiotensin II at the AT1 receptor between 2 and 4 weeks of age may be critically up-regulated by fetal factors, including exposure to glucocorticoids of maternal origin.

scholarly journals Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein dietin utero

2000 ◽  
Vol 83 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Margaret O. Nwagwu ◽  
Anna Cook ◽  
Simon C. Langley-Evans
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Urinary Albumin ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Fetal Life ◽  
Progressive Deterioration ◽  
Maternal Undernutrition ◽  
Low Protein

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CHD. Animal experiments suggest that the kidney, which is extremely vulnerable to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal haemodynamic functions following structural impairment in fetal life is proposed to require adaptations which raise systemic blood pressure and promote a more rapid progression to renal failure. Rats were fed on diets containing 180 g casein/kg (control) or 90 g casein/kg (low protein) during pregnancy. The offspring were studied in terms of blood pressure, creatinine clearance, blood urea N, plasma and urinary albumin, renal morphometry and metabolic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at all ages in the low-protein-exposed offspring, relative to control rats. Rats (4 weeks old) exposed to the low-protein diet had smaller kidneys which were shorter and wider than those of control animals. Creatinine clearance was significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenced by prenatal diet. Blood urea N, urinary output and urinary albumin excretion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a progressive deterioration of renal function in hypertensive rats exposed to mild maternal protein restriction during fetal life. This is consistent with the hypothesis that adaptations to maintain renal haemodynamic functions following impairment of fetal nephrogenesis result in an accelerated progression towards glomerulosclerosis and increased intrarenal pressures mediated by rising vascular resistance.

Effect of High-Salt, High-Carbohydrate, Low-Protein Diet on Hypertension in the Rat

1973 ◽  
Vol 45 (s1) ◽  
pp. 99s-102s
Author(s):  
Hideo Ueda
Keyword(s):  
Blood Pressure ◽  
High Protein Diet ◽  
Normal Diet ◽  
High Salt ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
High Carbohydrate ◽  
Low Protein

1. High-salt, high-carbohydrate and low-protein diet induces remarkable elevation of blood pressure in spontaneous hypertensive rats (SHR). 2. These animals have low serum potassium, low blood urea nitrogen and high blood sugar. 3. Heart weight is increased in proportion to the elevation of blood pressure. 4. Kidney weight of rats receiving the high-salt, high-carbohydrate and low-protein diet was, by contrast, smaller than SHR receiving a normal diet. 5. The kidneys of SHR receiving a high-salt, high-protein diet were twice as heavy as the kidneys of normal rats. 6. Similar dietary modifications in Goldblatt hypertensive rats to those in SHR produced similar changes in blood pressure and heart weight.

scholarly journals Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

2015 ◽  
Vol 308 (5) ◽  
pp. F411-F419 ◽  
Author(s):  
German Lozano ◽  
Ayah Elmaghrabi ◽  
Jordan Salley ◽  
Khurrum Siddique ◽  
Jyothsna Gattineni ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Control Group ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Mature Adult ◽  
Low Protein

The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group ( P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

scholarly journals Serum metabolites associated with dietary protein intake: results from the Modification of Diet in Renal Disease (MDRD) randomized clinical trial

2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Dietary Protein ◽  
Protein Intake ◽  
Filtration Rate ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Intake ◽  
Low Protein ◽  
P 16

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.

scholarly journals Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease

2007 ◽  
Vol 71 (3) ◽  
pp. 245-251 ◽  
Author(s):  
V. Bellizzi ◽  
B.R. Di Iorio ◽  
L. De Nicola ◽  
R. Minutolo ◽  
P. Zamboli ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein ◽  
Very Low Protein Diet

DOMINANT EFFECT OF SUPPLEMENTED-SUCROSE ON THE LOW PROTEIN DIET-INDUCED INCREASE IN BLOOD PRESSURE OF SPRAGUE-DAWLEY RATS

2001 ◽  
Vol 23 (7) ◽  
pp. 569-578
Author(s):  
Michiyo Endoh ◽  
Asako Kunieda ◽  
Takashi Yoneyama ◽  
Kazuhisa Ohishi ◽  
Akira Hishida ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Sprague Dawley ◽  
Dominant Effect ◽  
Low Protein ◽  
Sprague Dawley Rats

Weanling Rats Exposed to Maternal Low-Protein Diets during Discrete Periods of Gestation Exhibit Differing Severity of Hypertension

1996 ◽  
Vol 91 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Simon C. Langley-Evans ◽  
Simon J. M. Welham ◽  
Rachel C. Sherman ◽  
Alan A. Jackson
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Plasma Renin ◽  
Late Gestation ◽  
Protein Diet ◽  
Male Rats ◽  
Low Protein Diet ◽  
Fetal Exposure ◽  
Low Protein ◽  
Protein Diets

1. In the rat, hypertension is induced by fetal exposure to maternal low-protein diets. The effect on blood pressure of undernutrition before conception and during discrete periods in early, mid or late pregnancy was assessed using an 18% casein (control) diet and a 9% casein diet to apply mild protein restriction. 2. The offspring of rats fed 9% casein developed raised blood pressure by weaning age. Feeding a low-protein diet before conception was not a prerequisite for programming of hypertension. 3. Hypertension was observed in rats exposed to low protein during the following gestational periods: days 0–7, days 8–14 and days 15–22. Blood pressure increases elicited by these discrete periods of undernutrition were lower than those induced by feeding a low-protein diet throughout pregnancy. The effect in early gestation was significant only in male animals. Post-natal growth of male rats exposed to low-protein diets was accelerated, but kidneys were small in relation to body weight. 4. Biochemical indices of glucocorticoid action in liver, hippocampus, hypothalamus and lung were elevated in rats exposed to low-protein diets in utero. The apparent hypersensitivity to glucocorticoids was primarily associated with undernutrition in mid to late gestation. 5. Plasma renin activity was elevated in rats exposed to 9% casein over days 15–22 of gestation. Animals undernourished over days 0–7 and 8–14 produced pups with lower plasma angiotensin II concentrations at weaning. 6. Fetal exposure to maternal low-protein diets for any period in gestation may programme hypertension in the rat. Alterations to renal structure, renal hormone action or the hypothalamic—pituitary-adrenal axis may all play a role in the programming phenomenon, either independently or in concert.

scholarly journals A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but Not Nonpregnant Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Haijun Gao ◽  
Daren Tubianosa Tanchico ◽  
Uma Yallampalli ◽  
Chandrasekhar Yallampalli
Keyword(s):  
Angiotensin Ii ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Pregnant Rats ◽  
Low Protein ◽  
Plasma Angiotensin ◽  
Ace Activity

Pulmonary angiotensin II production is enhanced in pregnant rats fed a low-protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whetherAceexpression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions ofAceandAce2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression ofAceandAce2and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy.

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