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Prenatal programming results in an increase in blood pressure in adult offspring. We have shown that compared to control adult offspring whose mothers were fed a 20% protein diet, programmed adults whose mothers were fed a 6% protein diet during the last half of pregnancy have an increase in renal sympathetic nerve activity and urinary angiotensinogen/creatinine levels. We hypothesized that the increase in urinary angiotensinogen was mediated by renal sympathetic nerve activity in programmed rats. In this study performed in 3 month old rats, renal denervation resulted in normalization of blood pressure in the 6% programmed group (150 ± 3 Hg in 6% sham vs. 121 ± 4 Hg in 6% denervated, P < 0.001), and a reduction in blood pressure in the 20% group (126 ± 2 Hg 20% sham vs. 113 ± 4 Hg 20% denervated ( P < 0.05). We confirm that the intrarenal renin-angiotensin system assessed by urinary angiotensinogen/creatinine is upregulated in offspring of rats fed a 6% protein diet rats compared to 20% controls. To determine if sympathetic nerve activity was mediating the increase in urinary angiotensinogen in programmed rats, we compared denervated to sham-operated control and programmed rats. Renal denervation had no effect on urinary angiotensinogen/creatinine ratio in the 20% group and no effect on the increased urinary angiotensinogen/creatinine ratio found in programmed rats. This study demonstrates that the increase in urinary angiotensinogen in programmed rats is not mediated by renal sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

A maternal low-protein diet has been shown to program hypertension and a reduction in glomerular filtration rate in adult offspring. This study examined the effect of continuous administration of enalapril in the drinking water and transient administration of enalapril administered from 21 to 42 days of age on blood pressure and glomerular filtration rate (GFR) in male rats whose mothers were fed a 20% protein diet (control) or a 6% protein diet (programmed) during the last half of pregnancy. After birth all rats were fed a 20% protein diet. Programmed rats (maternal 6% protein diet) were hypertensive at 15 months of age compared to control rats and both continuous and transient administration of enalapril had no effect on blood pressure on control offspring, but normalized the blood pressure of programmed offspring. GFR was 3.2 ± 0.1 mL/min in the control group and 1.7 ± 0.1 mL/min in the programmed rats at 17 months of age (P < 0.001). The GFR was 3.0 ± 0.1 mL/min in the control and 2.7 ± 0.1 mL/min in the programmed group that received continuous enalapril in their drinking water showing that enalapril can prevent the decrease in GFR in programmed rats. Transient administration of enalapril had no effect on GFR in the control group (3.2 ± 0.1 mL/min) and prevented the decrease in GFR in the programmed group (2.9 ± 0.1 mL/min). In conclusion, transient exposure to enalapril for 3 weeks after weaning can prevent the hypertension and decrease in GFR in prenatal programmed rats. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundPrenatal programming of hypertension has been described in humans and in animal models that receive a prenatal insult, but the mechanism for the increase in blood pressure remains elusive.MethodsIn male rats whose mothers received dexamethasone between days 15 and 18 of gestation systemic and urinary levels of angiotensin II were measured to determine whether angiotensin II was a potential factor for the generation (4 weeks of age) or maintenance (8 weeks of age) of hypertension.ResultsA group 4- and 8-week-old male rats that were the product of a pregnancy where the mother received prenatal dexamethasone between days 15 and 18 of gestation had comparable plasma renin and angiotensin II levels to the offspring of vehicle-treated controls. Renal angiotensin II levels were not different at 4 and 8 weeks of age between the controls and the prenatal dexamethasone group. Urine angiotensin II/Creatinine levels, a reflection of filtered and renally generated and secreted angiotensin II, were higher at both 4 and 8 weeks of age in male rats that received prenatal dexamethasone compared to controls.ConclusionsThe high-urine angiotensin II levels in prehypertensive and hypertensive rats that were the product of mothers that received dexamethasone compared to vehicle suggest that luminal angiotensin II may play a role in the generation and maintenance of hypertension in this model of prenatal programming.American Journal of Hypertension 2010; doi:10.1038/ajh.2009.274 [ABSTRACT FROM AUTHOR]

Dagan A, Habib S, Gattineni J, Dwarakanath V, Baum M. Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone. Am J Physiol Re gut Integr Comp Physiol 297: R93-R99, 2009. First published April 29, 2009; doi: 10.1152/ajpregu.9 1006.2008.-Prenatal administration of dexamethasone and a low-protein diet has been shown to result in hypertension in the offspring when they are adults. The cause for the hypertension is unknown. The purpose of this study was to examine whether there was prenatal programming of thick ascending limb transport. Rats were administered either dexamethasone for 4 days (0.2 mg/kg body wt) by intraperitoneal injection daily between the 15th and 18th day of gestation, or they were fed a low-protein diet (6% protein) or an isocaloric normal protein diet (20% protein) from day 12 gestation until birth. The offspring were studied as adults. Prenatal dexamethasone and dietary protein deprivation resulted in an increase in blood pressure. Offspring of mothers fed a low-protein diet had an increase in medullaiy but not cortical bumetanide-sensitive Na-K-2C1 cotransporter (NKCC2) protein abundance (P < 0.01). There was not a statistically significant increase in medullary NKCC2 by prenatal dexamethasone (P = 0.07). Both prenatal administration of dexamethasone and a low-protein diet resulted in an increase in medullary thick ascending limb chloride transport compared with control (298 ± 33 pmoles∙mm[sup-1]∙min[sup-1], 280 ± 26 pmoles∙mm[sup-1]∙min[sup-1], and 191 ± 21 pmoles∙mm[sup-1]∙min[sup-1], respectively P < 0.05). There was a higher lumen-positive transepithelial potential difference in the prenatal dexamethasone and low-protein group compared with control as well. Administration of furosemide for 24 h resulted in a decrease in blood pressure in the low-protein group but not the control group. This study demonstrates that insults administered to the fetus can program altered sodium transport. Increased tubular sodium transport is a likely cause for the hypertension by prenatal programming. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that dexamethasone administered to pregnant rats during specific times during gestation results in a reduction in glomerular number and hypertension in offspring at 2 and 6 months of age. In this study, we examined the effect of prenatal dexamethasone administered daily on days 15 and 16 of gestation in male and female offspring after 1 year of age on glomerular filtration rate. The prenatal dexamethasone male group had a higher systolic blood pressure than the vehicle male group. Females had lower systolic blood pressures than the males and prenatal dexamethasone did not affect blood pressure in female offspring. Prenatal dexamethasone resulted in a reduction in glomerular filtration rate in male but not in female rats. When corrected for body weight, the control male rats had a lower glomerular filtration rate than the control female rats. Males had greater protein excretion than females and prenatal dexamethasone increased the protein excretion only in male rats. Glomerulosclerosis was also greater in male rats than females but was not affected by prenatal dexamethasone. In summary, male rats appear to have evidence of a decline in glomerular filtration rate after 1 year of age and prenatal dexamethasone programs an accelerated decline in glomerular filtration rate in male but not in female offspring. [ABSTRACT FROM AUTHOR]