Rat aortic endothelium antagonizes nitroprusside-induced relaxation by release of the peptide endothelin.

1. The effects of porcine endothelin were examined in rat thoracic aortic rings. 2. Endothelin was a potent contractile agonist (EC50 4.0 +/- 0.6 nmol/L). 3. Endothelin (1 nmol/L) did not affect contractile responses to cumulative concentrations of the thromboxane analogue, U46619. 4. In the presence of U46619, but not phenylephrine, endothelin (1 nmol/L) and endothelium abrogated the vasodilator response to cumulative concentrations of sodium nitroprusside. 5. The inhibitory effect of endothelin on vasodilator responses to nitroprusside in the presence of U46619 was abolished by nifedipine (0.1 mumol/L) but unaffected by indomethacin (3 mumol/L) or haemoglobin (10 mumol/L). 6. These data suggest that endothelin generated by native endothelium exerts a physiological antagonism of sodium nitroprusside in the presence of thromboxane.