Endothelin (ET-21) induced a sustained contraction of rat thoracic aortae (EC50 = 2.65 x 10(-10) M) in vitro, and caused a potent pressor effect in vivo after intravenous administration to rats. In contrast, the precursor deduced from porcine cDNA coding ET-21 (pET-39) had 100-fold less contractile activity in vitro (EC50 = 3.26 x 10(-8) M), and so did the precursor from human cDNA (hET-38) (EC50 = 1.48 x 10(-8) M). However, both pET-39 and hET-38 caused almost the same dose-dependent pressor effects as ET-21 in vivo. After intravenous bolus injection at 1 nmol/kg, ET-21 caused an initial transient drop of the arterial pressure, and then induced a gradual pressor effect. On the other hand, hET-38 caused only a gradual rise of the arterial pressure. There may be different mechanism(s) for ET-21 and hET-38 which induce changes in the arterial pressure in vivo.