Bradykinin, an important mediator of the cardiovascular effects of metallopeptidase inhibitors: experimental and clinical evidences

Journal of Clinical and Basic Cardiology 2001; 4 (1): 39-46

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Keywords: ACE-Hemmer,  bradykinin,  Kardioprotektion,  Vasopeptidasehemmer,  angiotensin I converting enzyme inhibitors,  bradykinin,  cardioprotection,  vasopeptidase inhibitors

Bradykinin (BK), a nanopeptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg), is the prototype of a family of powerful vasodilatory peptides, the kinins. Although known for a long time only as a pro-inflammatory peptide, BK is now considered an important mediator of the benefits of angiotensin I-converting enzyme inhibitors (ACEi). In fact, over the years, numerous papers have been dedicated to BK, and a number of them dealt with its cardiovascular effects. Different experimental and clinical arguments plead for a role of BK in the cardiovascular effects of ACEi. BK may also be an important mediator of a new class of drugs, vasopeptidase inhibitors. These single molecules simultaneously inhibit the activity of neutral endopeptidase 24.11 and angiotensin-converting enzyme, two kininases, with similar nanomolar inhibitory constants. The protective effect of omapatrilat, the first of this new class of drugs, on BK degradation at the cardiomyocyte and endothelial level, two target sites for metallopeptidase inhibitors, has also been documented and compared to that of ACEi. The purpose of this paper is to review the different experimental and clinical arguments that support a cardioprotective role of this vasodilatory peptide, BK. J Clin Basic Cardiol 2001; 4: 39-46.