Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anaesthetized rats

Intravenous injection of big endothelin-3 (big ET-3, 1-41 amide) at 3 nmol/kg to ganglion-blocked anaesthetized rats produced a long-lasting hypertensive action, but the action was less potent than that seen with the same dose of ET-3-(1-21). The pressor effect induced by big ET-3 was markedly attenuated by pretreatment with phosphoramidon, 5 mg/kg i.v., a dose which had no effect on the hypertensive action induced by ET-3. These results strongly suggest that big ET-3 is converted to mature ET-3 by a phosphoramidon-sensitive metalloproteinase in vivo, in a manner similar to the conversion of big ET-1 to ET-1.