kininases

Kininases are enzymes that degrade and inactivate kinins, peptide mediators generated in the kallikrein-kinin system. Kinins such as bradykinin and kallidin promote vasodilation, increased vascular permeability, and pain. Kininases therefore regulate the local and systemic actions of kinins, helping to limit inflammation and control blood pressure and fluid balance.

The classical classification distinguishes kininase I and kininase II. Kininase I is a carboxypeptidase that removes the C-terminal arginine from bradykinin and kallidin, producing inactive fragments such as bradykinin-(1-7) and kallidin-(1-7). Kininase II is primarily angiotensin-converting enzyme (ACE), a dipeptidyl carboxypeptidase that cleaves a dipeptide from the bradykinin C-terminus, inactivating bradykinin. ACE serves as a key link between the kinin and renin-angiotensin systems and metabolizes several other peptides as well.

Beyond these two, other enzymes contribute to kinin degradation. Neutral endopeptidase (neprilysin) and various aminopeptidases can cleave kinins or their fragments, reducing kinin signaling in a tissue-dependent manner. The kininase network is widespread, with activity that varies by tissue, physiological state, and disease.

Clinical relevance centers on the interplay between kininases and pharmacology. ACE inhibitors used to treat hypertension and heart failure reduce kininase II activity, leading to increased bradykinin levels that contribute to drug-induced vasodilation but can also cause cough or angioedema in some patients. Understanding kininase activity informs perspectives on edema, inflammation, and cardiovascular therapeutics.