Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor effect in vivo

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Abstract
Endothelin (ET‐21) induced a sustained contraction of rat thoracic aortae (EC50=2.65 × 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 × 10−8M), and so did the precursor from human cDNA (hET‐38) (EC50=1.48 × 10−8M). 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.