In the present study, the pressure-natriuretic responses of 3- to 5- and 6- to 9-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were characterized to determine whether the relationship between sodium excretion and renal perfusion pressure is altered during the development of hypertension. Differences in the neural tone and renal hormone levels in SHR and WKY were minimized by denervating the kidney and fixing plasma concentrations of aldosterone, vasopressin, norepinephrine, and cortisol by intravenous infusion. Renal perfusion pressure was varied using adjustable occluders on the lower aorta. The slopes of the relationships between sodium excretion and renal perfusion pressure were not significantly different in 3- to 5-week-old SHR and WKY (0.31 +/- 0.05 vs 0.42 +/- 0.06 microEq/min/g kidney weight); however, the x-intercept of this relationship was significantly shifted to the right by 15 mm Hg in SHR compared to WKY. Blood pressure was moderately elevated even in the 3- to 5-week-old SHR in comparison to WKY (98 +/- 5 vs 81 +/- 6 mm Hg). As the degree of hypertension became more severe, the slope of the pressure-natriuresis relationship became significantly lower in 6- to 9-week-old SHR compared to the corresponding slope observed in age-matched WKY (0.16 +/- 0.02 vs 0.31 +/- 0.04 microEq/min/g kidney weight). These results indicate that the relationship between sodium excretion and renal perfusion pressure is altered even in very young SHR. Thus, the resetting of kidney function occurs very early and may be necessary for the development of hypertension in SHR.