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Prenatal programming of adult hypertension in the rat
V M Vehaskari1, D H Aviles, J Manning
1Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. vvehas@lsuhsc.edu
Insights
Maternal low-protein diet during pregnancy can program offspring for adult hypertension. This may be due to fewer nephrons and altered hormone levels, impacting kidney development and blood pressure regulation.
Area of Science:
- Developmental Biology
- Nephrology
- Endocrinology
Background:
- Epidemiological studies link low birth weight to adult essential hypertension.
- The underlying mechanisms for this association remain largely unknown.
Purpose of the Study:
- To investigate the impact of maternal low-protein diet on offspring blood pressure and kidney development in a rat model.
- To explore potential mechanisms linking prenatal nutrition to adult hypertension.
Main Methods:
- A rat model of intrauterine growth retardation was established using a 6% protein diet for pregnant dams.
- Offspring blood pressure, apoptosis, cell proliferation, and glomeruli number were assessed.
- Renin-angiotensin-aldosterone system (RAAS) components were analyzed.
Main Results:
- Low-protein offspring exhibited reduced kidney size and a 28-29% deficit in total glomeruli number.
- Offspring developed significantly higher systolic blood pressure (20-25 mm Hg) by eight weeks of age.
- Prehypertensive offspring showed suppressed plasma renin activity (PRA) and elevated aldosterone levels.
Conclusions:
- Prenatal exposure to maternal low-protein diet programs adult hypertension in rats.
- A reduced nephron number and an altered renin-aldosterone axis are potential mechanisms involved.
- This study highlights the critical role of maternal nutrition in long-term offspring cardiovascular health.
Background:
Epidemiological studies have suggested that low birthweight is a risk factor for the development of essential hypertension in adulthood, but the mechanism is unknown.
Methods:
A rat model of intrauterine growth retardation was employed. Pregnant Sprague-Dawley rats were kept on 6% protein or on control isocaloric 20% protein diet from gestational day 12 until term. Systolic blood pressures of the offspring were monitored by the tail cuff method. Apoptosis was determined by the TUNEL method, cell proliferation by anti-Ki67 antibody, and the total number of glomeruli by the maceration method. Results are mean +/- SD.
Results:
The kidney and body sizes of the offspring from the low-protein pregnancies (LP) were proportionately decreased at birth. Full catch-up growth occurred during the first two weeks of life. The kidneys were normal by standard histology but exhibited increased apoptosis without increased cell proliferation at eight weeks of age. The total number of glomeruli per kidney was decreased by 28% in males (P < 0.001) and by 29% in females (P < 0.01). By eight weeks of age, both male and female LP had systolic blood pressures that were 20 to 25 mm Hg higher than those of control animals (P < 0.001), and their 18-month survival was significantly decreased (44 vs. 93%, P < 0.01). During the prehypertensive stage, at four weeks of age, PRA in LP was low (1.7 +/- 1.4 vs. 19.7 +/- 5.5 ng/mL/hour in males, P < 0.0001; 4.9 +/- 2.2 vs. 14.9 +/- 7.2 ng/mL/hour in females, P < 0.0005), and aldosterone was high (93 +/- 15 vs. 54 +/- 27 pg/mL in males, P < 0. 005; 93 +/- 20 vs. 48 +/- 20 pg/mL in females, P < 0.0001). Smaller but significant differences persisted at eight weeks of age.
Conclusions:
Adult blood pressure profile is susceptible to prenatal programming by maternal low-protein diet in the rat. The mechanism may involve an altered renin-aldosterone axis and a deficit in total nephron number.