New perspectives on the origin of hypertension; the role of the hypothalamic melanocortin system

New Findings What is the topic of this review? The growing epidemic of obesity has attracted increasing interest in the effect of obesity in pregnancy on the developing child. Independent associations have been reported between maternal obesity and hypertension in the offspring. This review focuses on novel advances in our comprehension of sympathetically mediated hypertension. What advances does it highlight? Our recent studies have unravelled important mechanisms of leptin and the melanocortin system in the early origins of hypertension. Offspring of obese dams have a heightened arterial pressure response to leptin, which is normalized by central administration of melanocortin receptor antagonist. The central melanocortin system may contribute to the elevated arterial pressure in juvenile offspring secondary to maternal obesity. Maternal obesity is a major public health problem. Pregnant obese women have increased risk of adverse outcomes for mother and child. Recent observational studies from mother–child cohort studies suggest that obesity during pregnancy is a risk factor for the development of cardiovascular diseases in the child later in life. We have previously shown that maternal obesity in rodents leads to sympathetically mediated hypertension in the juvenile offspring prior to obesity. This was associated with an exaggerated leptin surge in early postnatal life. Increased leptin during this critical period of development is likely to contribute to the onset of hypertension by altered leptin sensitivity and dysregulation of the normal neurotrophic action of leptin. Unpublished evidence also suggests that the central melanocortin system, including melanocortin 4 receptors, plays a key role in early origins of hypertension in offspring of obese rat dams. This review focuses on the role of the central leptin–melanocortin signalling pathways in the early origins of hypertension. The overall aim is to understand the central leptin–melanocortin system, with its multiple intracellular signalling pathways which differentially and independently regulate appetite, renal sympathetic nerve activity and blood pressure.