title: Renal and extrarenal mechanisms of perinatal programming after intrauterine growth restriction.
abstract: The concept of fetal programming of disease in later life after intrauterine growth restriction (IUGR) has opened a potential new perspective on the treatment and prevention of arterial hypertension. Numerous large studies have recently confirmed the relationship between low birth weight and raised blood pressure. Hyperalimentation after birth appears to add to the risk of higher blood pressure later in life. However, there is still a controversy and clear intervention studies have not yet been possible. Therefore, the gain of knowledge about the underlying mechanisms of fetal programming is of utmost importance.Two major groups of mechanisms may be identified: renal and extrarenal mechanisms. Renal mechanisms include the reduction of nephron number, which is encountered in patients and animals with low birth weight. According to the so-called Brenner hypothesis, this may lead to increased arterial blood pressure. Another important renal system is the renin-angiotensin-aldosterone system, which appears to be more active on a number of levels in low birth weight individuals. Finally, there is the conversion of cortisol to inactive cortisone by the 11beta-hydroxysteroid dehydrogenase in distal tubule cells, which is reduced after intrauterine growth restriction. This enables a more powerful activation of mineralocorticoid receptors by cortisol. Extrarenal mechanisms include alterations in vascular structure (primary and secondary), increased activity of the sympathetic nerve system, and maybe most interestingly, an impairment of endothelial function. The latter is at least partially caused by an inactivation of nitric oxide by an excess of free oxygen radicals. In summary, mechanisms of fetal programming are only in the process of being revealed, and research has to focus on finding the key mechanism that might allow for successful intervention.
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany. joerg.doetsch@uk-erlangen.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D005333:Fetus / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007231:Infant, Newborn; D007668:Kidney / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects