EVIDENCE FOR PHOSPHORAMIDON-SENSITIVE CONVERSION OF BIG ENDOTHELIN-1 TO ENDOTHELIN-1 IN ISOLATED RAT MESENTERIC-ARTERY

The effect of phosphoramidon, a metalloproteinase inhibitor, on the pressor respose to big endothelin-1 (big ET-1) in the isolated perfused rat mesenteric artery was examined. Big ET-1 (10-9-10-7 M) caused a concentration-dependent increase in the perfusion pressure. The pressor response was markedly suppressed by phosphoramidon (10-5 M). The inhibitor did not influence the ET-1 (5 × 10-11-10-8 M)-induced pressor action. Big ET-1 (5 × 10-8 M)-induced pressor action was accompanied by an increase in immunoreactive (IR)-ET in the perfusate, and this increase was suppressed by the addition of phosphoramidon. IR-ET in the perfusate was confirmed to be ET-1, as determined by reverse-phase HPLC. These findings strongly suggest that phosphoramidon-sensitive metalloproteinase contributes to the conversion of big ET-1 to ET-1, in vivo. © 1991.