The effects of novel cathepsin E inhibitors on the big endothelin pressor response in conscious rats

The aspartic protease, Cathepsin E, has been shown to specifically cleave big endothelin (big ET-1) at the Trp21-Val22 bond to produce endothelin (ET-1) and the corresponding C-terminal fragment. To determine whether Cathepsin E is a physiologically relevant endothelin converting Enzyme (ECE), three novel and potent inhibitors of Cathepsin E were administered to conscious rats prior to a pressor challenge with big ET-1. One of the inhibitors of Cathepsin E, SQ 32,056 (3 mg/kg i.v.), blocked the big ET-1 response. However, this dose of SQ 32,056 also blocked the pressor response to ET-1. Phosphoramidon specifically inhibited the Big ET-1 pressor response. These results suggest that ECE is not Cathepsin E.