Perinatal development and adult blood pressure.

N Ashton

doi:10.1590/s0100-879x2000000700002

Abstract

A growing body of evidence supports the concept of fetal programming in cardiovascular disease in man, which asserts that an insult experienced in utero exerts a long-term influence on cardiovascular function, leading to disease in adulthood. However, this hypothesis is not universally accepted, hence animal models may be of value in determining potential physiological mechanisms which could explain how fetal undernutrition results in cardiovascular disease in later life. This review describes two major animal models of cardiovascular programming, the in utero protein-restricted rat and the cross-fostered spontaneously hypertensive rat. In the former model, moderate maternal protein restriction during pregnancy induces an increase in offspring blood pressure of 20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to excess maternal glucocorticoids as a result of a deficiency in placental 11-ss hydroxysteroid dehydrogenase type 2. Furthermore, nephrogenesis is impaired in this model which, coupled with increased activity of the renin-angiotensin system, could also contribute to the greater blood pressure displayed by these animals. The second model discussed is the cross-fostered spontaneously hypertensive rat. Spontaneously hypertensive rats develop severe hypertension without external intervention; however, their adult blood pressure may be lowered by 20-30 mmHg by cross-fostering pups to a normotensive dam within the first two weeks of lactation. The mechanisms responsible for this antihypertensive effect are less clear, but may also involve altered renal function and down-regulation of the renin-angiotensin system. These two models clearly show that adult blood pressure is influenced by exposure to one of a number of stimuli during critical stages of perinatal development.

Highlights

The concept of fetal programming in cardiovascular disease is controversial, despite the abundance of epidemiological data supporting this notion
Individuals who came from areas with high infant mortality rates were much more likely to suffer from cardiovascular disease in adulthood
The fetus is normally protected from the high circulating levels of maternal glucocorticoids by the enzyme 11-ß HSD type 2 which converts corticosterone to 11-dehydrocorticosterone in the rat. Activity of this enzyme positively correlates with birth weight in both the rat [20] and man [21], suggesting that it may play a role in regulating fetal growth and development of cardiovascular disease in adulthood. This hypothesis is supported by the observation that maternal protein restriction during pregnancy in the rat results in diminished placental 11-ß HSD type 2 activity and increased exposure of the fetus to maternal glucocorticoids, which was associated with increased blood pressure in adulthood [22]

Summary

Introduction

The concept of fetal programming in cardiovascular disease is controversial, despite the abundance of epidemiological data supporting this notion. In the former model, moderate maternal protein restriction during pregnancy induces an increase in offspring blood pressure of 20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to excess maternal glucocorticoids as a result of a deficiency in placental 11-ß hydroxysteroid dehydrogenase type 2.

Results

Conclusion