Blocking kinin-processing enzyme eases angiotensin II hypertension in mice
- Kininase I (carboxypeptidase N) converts bradykinin and kallidin into des-Arg kinins, the main agonists of the B1 receptor, linking kinin signalling to vasoconstriction and inflammation.
- In mice given chronic angiotensin II, loss of CPN gene function dampened the rise in blood pressure, B1 receptor expression, sympathetic drive and cardiac fibrosis.
- Treating normal mice with the kininase I inhibitor Mergetpa similarly lowered blood pressure, limited B1 receptor up-regulation, and reduced complement activation and immune cell infiltration.
💡 Points Based on the abstract
CPN sits upstream of B1 signaling, so hitting it is a cleverly indirect way to tame an induced receptor. But carboxypeptidase N is broad: it also trims anaphylatoxins and other peptides, so safety is my worry. Angiotensin II mice and a single tool inhibitor don't show clinical relevance. I'd want selectivity, exposure data and a second hypertension model first.