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

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 Unpublished evidence also suggests that the central melanocortin system, including melanocortin 4 receptors, plays a key role in early origins of hypertension in offspring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.