ObjectiveTo study the possible involvement of intrarenal endothelial dysfunction in the modulation of the pressure-natriuresis curve in spontaneously hypertensive rats (SHR).Methods: Weexamined the effect of endothelin on pressure natriuresis in isolated perfused kidneys from 16-week-old SHR and Wistar-Kyoto (WKY) rats. Plasma and urinary endothelin levels in intact rats and the rate of endothelin release from isolated kidneys were also determined.ResultsUrinary sodium excretion by SHR kidneys was 60% less than by WKY rat kidneys at a given perfusion pressure. Endothelin-1 increased the renal vascular resistance dose-dependently and the change was comparable in SHR and WKY rats. A high perfusate concentration of endothelin-1 markedly reduced urinary sodium excretion, resulting in a significant rightwards shift of the pressure-natriuresis curve. However, endothelin-1 at concentrations below 0.1 nmol/l did not decrease urinary sodium excretion, despite its renal vasoconstrictory activity. In a differentin vivostudy, plasma endothelin-like immunoreactivity was similar in the two groups, as was the urinary endothelin excretion. However, the rate of endothelin release from isolated SHR kidneys was slightly greater than from WKY rat kidneys.ConclusionSince the difference in endothelin levels is not remarkable, it seems unlikely that increased intrarenal production of endothelin plays a role in the maintenance of hypertension in SHR by modulating the pressure-natriuresis curve.