These findings support previous studies where omapatrilat increased fluid and protein permeability in cat skeletal muscle through BK-dependent processes45 and corroborate clinical data where omapatrilat caused unexpected tissue swelling and angioedema.22,23 Putative underlying processes have been attributed to inhibition of the breakdown of BK and substance P by ACE and aminopeptidases.13,46 Here, we observed that mice treated with LisW-S+sacubitril, but not omapatrilat, had increased BK 1-5 levels, indicating effective BK metabolism. This evidence concerns the gene CPQ and angioedema.