Barker and Brenner: A Basis for Hypertension?

Karen   M.   Moritz; John   F.   Bertram

Abstract

In the large majority of cases, the underlying cause of hypertension is unknown. In the late 1980 ’ s, Barry Brenner and colleagues suggested that individuals with a reduced nephron endowment were more likely to develop hypertension. This was followed soon after by the report from epidemiologist, David Barker and co-workers, of a link between low birth weight and an increased risk of adult cardiovascular disease, including hypertension. It was proposed that a low birth weight was indicative of a fetus having been exposed to a suboptimal intrauterine environment and somehow being "programmed" to develop adult disease. What is the evidence for a link between these two hypotheses, and does low birth weight, associated with a decrease in nephron endowment, provide in part, a basis for essential hypertension? In the past 20 years, intensive clinical and basic research has attempted to answer these questions using a variety of approaches. In normal human populations, low birth weight has been correlated with a low nephron number and both these factors have been shown to be associated with elevated blood pressure in adulthood. Animal models, especially those employing maternal protein deficiency or glucocorticoid exposure, have in general reproduced this phenomenon with offspring born of low birth weight having a reduced nephron number and hypertension in adulthood. However, experimental evidence is accumulating that low birth weight and a reduction in nephron endowment can occur independently of one another and do not always result in adult hypertension. In particular, the timing and nature of the in utero insult, the gender of the fetus and the subsequent postnatal environment may modify the outcome significantly.

Keywords: Developmental programming, kidney, nephron endowment