In freely moving rats, endothelin-1 (0.0135-4.5 nmol/kg) administered as an intravenous bolus injection, produced an immediate, short-lasting, dose-related fall in blood pressure followed by a long-lasting, dose-related increase in blood pressure. There was a higher sensitivity in the pressor responses to endothelin-1, in spontaneously hypertensive (SH) rats (ED(50) = 0.11 +/- 0.02 and 0.28 +/- 0.02 nmol/kg, in SH and normotensive rats, respectively), but no change in the maximal pressor effect of endothelin-1 in SH rats. In rat isolated aorta, endothelin-1 induced a greater vasocontractile effect in SH rats than in normotensive rats. In both rat strains, removal of the endothelium did not change the concentration-effect curves obtained in endothelium-intact preparations. These data add further support to the hypothesis that endothelin-1 could play a role in genetic hypertension, at least in the maintenance of high blood pressure.
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