DIFFERENCES IN POTENCY OF BIG ENDOTHELIN-1-INDUCED PRESSOR ACTION IN RAT ISOLATED-PERFUSED MESENTERIC-ARTERY, HINDQUARTER AND LUNG

We compared the pressor response to endothelin-1 (ET-1) with that of b ig endothelin-1 (big ET-1) in mesenteric arteries, hindquarters and lu ngs of rats. In these three preparations, both peptides caused a conce ntration-dependent increase in the perfusion pressure. The ratio of bi g ET-1 concentration to ET-, 1 concentration needed for causing the sa me pressor action is different between organs; i.e., a mesentery >> a hindquarter greater-than-or-equal-to a lung. Exposure to phosphoramido n, a metalloproteinase inhibitor, significantly suppressed the pressor response to big ET-1, in a similar fashion. This suppression is likel y to be due to the inhibition of phosphoramidon-sensitive endothelin c onverting enzyme, since the inhibitor does not suppress an action of E T-1. Apparently there is a difference in potency for phosphoramidon-se nsitive vasoconstriction of big ET-1 between organs and presumably reg ional differences in the functional phosphoramidon-sensitive conversio n of big ET-1 in vasculatures.