Several studies of adverse intrauterine conditions showing programmed hypertension in the offspring, including maternal obesity, also reported a peripheral vasoconstrictor phenotype in the offspring, including reduced endothelium-dependent relaxation36,45 with impaired nitric oxide bioavailability,7,28,36 dysregulation of the renin–angiotensin system,46 and sympathetic over-activation driven by maternal hyperleptinaemia.47 This evidence concerns the gene REN and hypertensive disorder.