7 In humans, persistent normotension after receiving a kidney graft from a normotensive donor was

observed in dialysis-dependent patients suffering from ‘essential hypertension’.8 These studies suggest that ‘blood pressure Palbociclib purchase goes with the kidney’. It has recently been recognized that maternal problems during pregnancy, for example nutritional deprivation, placental malfunction, hyperglycaemia, smoking and others, affect prenatal programming and predispose in postnatal life to hypertension, renal disease, metabolic syndrome and other sequelae.9 Specifically, Brenner postulated that nephron underdosing as a consequence of prenatal developmental problems is associated with hypertension and higher susceptibility to renal damage.10 Indeed, several studies11,12 documented lower numbers of glomeruli but larger glomerular size in hypertensive as compared to normotensive Caucasoid individuals. Low birthweight is known to be associated with reduced nephron numbers.13 Children with low weight at birth have low blood pressure at birth; at the end of the first postnatal year, however, their blood pressure values are within the highest percentile14 and at higher age an inverse correlation between birthweight and systolic blood pressure has recently been documented.15 It is of importance that in contrast to low nephron numbers at birth, reduction

of nephron numbers in adult life, for example by life-kidney donation, causes minimal – if any – increase in blood pressure.16 Metformin It is of

considerable importance with respect to the following discussion that a history of low birthweight is associated with salt sensitivity of blood pressure in healthy adult individuals.17 Arthur Guyton was the first to provide a quantitative mathematical explanation for the relation between blood pressure Pyruvate dehydrogenase lipoamide kinase isozyme 1 and natriuresis (pressure–natriuresis relationship).18,19 He postulated that if the pressure relationship is normal, salt intake would transiently raise arterial pressure which in turn would increase sodium excretion until the baseline steady-state pressure was reached. When the blood pressure/natriuresis relationship is shifted to the right, higher blood pressure values are required to enable the kidney to excrete sodium loads. It is very difficult in humans to carry out long-term studies examining the relationship between salt intake and blood pressure as well as cardiovascular end-points, respectively. The difficulty of large observational human studies is illustrated by the controversial results of the Intersalt study.20,21 Against this background, it is of interest that recently in chimpanzees changes in salt intake corresponding to intakes in humans resulted in significant long-term effects on blood pressure.