K. Hisaki et al., ENDOTHELIUM-INDEPENDENT PRESSOR EFFECT OF BIG ENDOTHELIN-1 AND ITS INHIBITION BY PHOSPHORAMIDON IN RAT MESENTERIC-ARTERY, European journal of pharmacology, 241(1), 1993, pp. 75-81
We asked whether or not the endothelium plays a functional role in the
conversion of big endothelin-1 to endothelin-I in the perfused rat me
senteric artery. In endothelium-denuded preparations, big endothelin-1
produced a much more potent pressor effect than in intact preparation
s. Phosphoramidon suppressed the big endothelin-1-induced pressor acti
on without affecting the action of endothelin-1, irrespective of the p
resence or absence of the endothelium. The amounts of immunoreactive-e
ndothelin in the perfusate during perfusion of endothelium-denuded pre
parations with big endothelin-1 were extremely low compared with those
observed in intact preparations and were not significantly suppressed
by the metalloproteinase inhibitor, phosphoramidon, in contrast to th
e case with intact preparations. When synthetic endothelin-1 was perfu
sed in the endothelium-denuded mesentery, the peptide disappeared from
the perfusate more rapidly than with intact preparations, suggesting
that endothelin-1 generated from big endothelin-1 is effectively trapp
ed by vascular smooth muscle cells in the endothelium-denuded preparat
ion. Our results suggest that the endothelium is not essential for the
conversion of big endothelin-1 to endothelin-1, in rat mesenteric art
ery.