Since the pathogenesis of essential hypertension is multifactorial, the causal therapy of primary arterial hypertension remains a great challenge. At a given genetic predisposition, the manifestation of hypertension depends critically on lifestyle factors. It is thus essential to study the molecular consequences of various deleterious lifestyle factors. We demonstrated by radiotelemetric measurements that an increased caloric intake raises both systolic and diastolic blood pressure as well as heart rate in spontaneously hypertensive rats (SHR). This model is comparable to hyperkinetic hypertension in hypertensive persons which, if it persists, will lead to established hypertension. Overfeeding also results in the characteristic metabolic derangements (hyperinsulinemia, hypertriglyceridemia) of insulin resistant hypertensive persons. The enhanced sympathetic outflow of the brain can be potentiated by lifestyle factors such as high sodium intake and psychological stress. In contrast to sodium intake, psychological stress (e.g. schedule-induced stress) is difficult to mimic in animal experiments. In view of the recent progress in the characterization of imidazoline receptors in the rostral ventrolateral medulla and the development of antihypertensive drugs with a high selectivity (moxonidine) for imidazoline receptors, efforts should be made to elucidate key regulatory mechanisms involved in brain insulin sensitivity and appetite regulation. Such an approach could help in pharmacologically reducing the influence of deleterious lifestyle factors at a given genetic predisposition.