EXPERIMENTAL-MODELS OF HYPERTENSION - ARE THEY MODELS FOR ESSENTIAL-HYPERTENSION IN MAN

Since the pathogenesis of essential hypertension is multifactorial, th e causal therapy of primary arterial hypertension remains a great chal lenge. at a given genetic predisposition, the manifestation of hyperte nsion depends critically on lifestyle factors. It is thus essential to study the molecular consequences of various deleterious lifestyle fac tors. We demonstrated by radiotelemetric measurements that an increase d caloric intake raises both systolic and diastolic blood pressure as well as heart rate in spontaneously hypertensive rats (SHR). This mode l is comparable to hyperkinetic hypertension in hypertensive persons w hich, if it persists, will lead to established hypertension. Overfeedi ng also results in the characteristic metabolic derangements (hyperins ulinemia, hypertriglyceridemia) of insulin resistant hypertensive pers ons. The enhanced sympathetic outflow of the brain can be potentiated by lifestyle factors such as high sodium intake and psychological stre ss. In contrast to sodium intake, psychological stress (e.g. schedule- induced stress) is difficult to mimick in animal experiments. In view of the recent progress in the characterization of imidazoline receptor s in the rostral ventrolateral medulla and the development of antihype rtensive drugs with a high selectivity (moxonidine) for imidazoline re ceptors, efforts should be made to elucidate key regulatory mechanisms involved in brain insulin sensitivity and appetite regulation. Such a n approach could help in pharmacologically reducing the influence of d eleterious lifestyle factors at a given genetic predisposition.