Mechanisms of Renal Programming and Cardiorenal Endowment

Much data support the concept that while alterations and restrictions in nutrition during gestation, or exposure to certain substances and medications during pregnancy may not result in major malformation, their long‐term effects may be substantial, leading to a propensity for the offspring to develop hypertension, cardiovascular disease, proteinuria and altered renal function in adult life. Recently, it has become evident that hypertension and renal dysfunction may be related to events from the past, as far back as intrauterine life, a concept that includes perinatal programming or developmental origins of health and disease. The concept that nephron number may strongly influence blood pressure as well as susceptibility to renal disease in later life developed in parallel with that of perinatal programming. Reviewing the evidence that supports these two concepts together may help elucidate, at least in part, the pathogenesis of not only primary but secondary hypertension. This talk will consider various experimental models that alter maternal exposures‐‐ maternal protein restriction, maternal steroid exposure, and changes in maternal ingestion of iron, retinols, or steroids. These exposures will be considered in the framework of nephrogenesis, discussing links between alterations in nephrogenesis and subsequent renal function and hypertension. The appeal of perinatal programming is that, unlike genetic factors, the impact of less than adequate maternal nutrition or certain drug or environmental exposures may be potentially addressable. Present research is beginning to clarify certain aspects of perinatal programming that may be approached by broad educational programs or therapeutic intervention.