Towards understanding the kallikrein-kinin system: insights from measurement of kinin peptides

The kallikrein-kinin system is complex, with several bioactive peptides tha t are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation o f blood pressure and sodium homeostasis, inflammatory processes, and the ca rdioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the functio n of the kallikreinkinin system. The levels of kinin peptides in tissues we re higher than in blood, confirming the primary tissue localization of the kallikreinkinin system. Moreover, the separate measurement of bradykinin an d kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide lev els were increased in the heart of rats with myocardial infarction, in tiss ues of diabetic and spontaneously hypertensive rats, and in urine of patien ts with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, bu t not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (A CE) and neutral endopeptidase (NEP) inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide leve ls in blood, urine, and tissues, which may be accounted for by the differen tial contributions of ACE and NEP to kinin peptide metabolism in the multip le compartments in which kinin peptide generation occurs. Measurement of th e levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology an d disease states.