Developmental origins of adult hypertension: new insights into the role of the kidney

Abstract

It is now accepted that early life environment can modulate adult phenotype. One of the best documented examples is the effect of prenatal environment on adult hypertension and cardiovascular morbidity. Human epidemiologic studies have been complemented with experimental models showing, for example, that maternal dietary manipulations during pregnancy in the rat can be used to induce adult hypertension in the offspring. The weight of the emerging evidence suggests that abnormal Na handling by the kidney plays an important role in the pathogenesis of the hypertension. Although the number of nephrons is modestly reduced in most experimental models, there is very little change in total glomerular filtration rate, casting doubt on the hypothesis that restricted Na filtration is the major mechanism. Recent studies have instead strongly suggested that renal tubular handling of Na is altered, resulting in an altered set-point for Na balance. The mechanism may involve intrarenal inflammation and increased oxidative stress which disrupt the tubulointerstitial microenvironment, leading to constitutively upregulated Na reabsorption in the distal tubule. The upregulation may be mediated by autocrine and paracrine factors promoting distal tubule Na reabsorption. A similar mechanism has been hypothesized to be important in other types of hypertension and may hence be a common pathway in the genesis of volume-dependent hypertension.