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Low birth weight-associated adult hypertension in the rat
1Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Insights
Maternal low-protein diet in rats caused low birth weight and adult hypertension. This condition, linked to intrauterine growth retardation, may involve sodium retention and expanded extracellular volume.
Area of Science:
- Developmental Biology
- Cardiovascular Physiology
- Nutritional Science
Background:
- Intrauterine growth retardation (IUGR) is a suspected risk factor for adult hypertension.
- Maternal nutrition significantly impacts fetal development and long-term health outcomes.
- Understanding the mechanisms linking IUGR to hypertension is crucial for preventative strategies.
Purpose of the Study:
- To investigate the relationship between low birth weight, induced by maternal dietary protein restriction, and the development of hypertension in adult rats.
- To explore the physiological changes associated with hypertension in this IUGR rat model.
- To assess the efficacy of angiotensin-converting enzyme (ACE) inhibition in managing hypertension and mortality in this model.
Main Methods:
- Induction of IUGR in Sprague-Dawley and Wistar rats via a maternal low-protein diet during the second half of gestation.
- Monitoring of birth weight, growth, blood pressure, and survival rates up to 11 months.
- Analysis of plasma creatinine, sodium concentration, and renin activity, along with assessment of proteinuria.
- Treatment with enalapril (an ACE inhibitor) initiated at 8 weeks of age.
Main Results:
- Offspring exhibited 15% lower birth weights but achieved catch-up growth by 4 weeks.
- Both male and female rats developed progressive hypertension starting at 8 weeks, with a reduced 11-month survival rate (69%).
- Early hypertension showed normal renal function, suppressed plasma renin activity, and mild proteinuria in males; plasma renin activity later increased.
- Enalapril normalized blood pressure but did not fully prevent increased mortality.
Conclusions:
- Maternal low-protein diet is a viable model for inducing low birth weight and subsequent adult hypertension in rats.
- Primary sodium retention and expanded extracellular volume are implicated as critical factors in the hypertension development.
- ACE inhibition is effective in controlling blood pressure in this model, but long-term survival benefits require further investigation.
Abstract:
Epidemiological surveys have suggested that intrauterine growth retardation is a risk factor for the development of hypertension in later life. A rat model of intrauterine growth retardation, induced by maternal low-protein diet during the second half of pregnancy, was used to study the relationship between birth weight and adult hypertension. The offspring were born at term and were allowed to nurse normally until weaned to standard chow at 4 weeks of age. They had 15% lower birth weights than control offspring, with complete catch-up growth by age 4 weeks. Both females and males developed progressively worsening hypertension beginning at 8 weeks. The 11-month survival rate was 69% versus 100% in control animals. During the early stages of the hypertension, plasma creatinine was normal, plasma sodium concentration was slightly higher than that of control animals, plasma renin activity was suppressed, and the males had mild proteinuria. Renal function remained normal throughout the 11-month observation period, but plasma renin activity gradually rose above control values. Angiotensin-converting enzyme inhibition by enalapril, begun at 8 weeks of age, was effective in completely normalizing the blood pressure, but did not totally prevent the extra mortality. Sprague-Dawley and Wistar rat strains developed equally severe hypertension after maternal protein deprivation, despite their different susceptibilities to nephrosclerosis with aging. In conclusion, maternal low-protein diet resulted in low birth weight and adult hypertension in the rat. Primary sodium retention and expanded extracellular volume may be critical factors during the development of the hypertension.