Interaction between sodium and angiotensin II: role of dose and duration of treatment

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Abstract
For understanding of human essential hypertension, experimental models are needed whereby a small, pathophysiologically relevant stimulus (dose) is applied for a long period of time (time-dependence). The upper limit of pathophysiologically relevant doses of ANG II and dietary sodium supplementation in rats appears to be 125 ng/kg/min sc and 2% NaCl, respectively. Circulating ANG II and dietary sodium may interact in the pathogenesis of hypertension on the vascular level by direct local action and by way of sympathetic stimulation. Modulation of angiotensin T1 receptors and vascular endothelin production have a lesser role in the interaction, if any, as long as ANG II administration and dietary sodium supplementation are kept in the pathophysiologically relevant range. The administration of ANG II and of dietary sodium supplementation in small doses but over long periods of time promises to be a fruitful experimental approach toward understanding human essential hypertension.