The kallikrein-kinin system in humans

1. Kinin peptides are implicated in many physiological and pathological processes, including the regulation of blood pressure and sodium homeostasis, inflammation and the cardioprotective effects of preconditioning. In humans, the plasma and tissue kallikrein-kinin systems (KKS) generate bradykinin and kallidin peptides, respectively. 2. We established methodology for the measurement of bradykinin and kallidin peptides and their metabolites in order to study the function of the plasma and tissue KKS in humans. 3. Bradykinin peptides were more abundant than kallidin peptides in blood and cardiac atrial tissue, whereas kallidin peptides were predominant in urine. The levels of kinin peptides in tissue were higher than in blood, confirming the primary tissue localization of the KKS. 4. Angiotensin-converting enzyme inhibition increased blood levels of bradykinin and kallidin peptides. 5. Blood levels of kallidin peptides were suppressed in patients with severe cardiac failure, indicating that the activity of the tissue KKS is suppressed in this condition. 6. Bradykinin peptide levels were increased in the urine of patients with interstitial cystitis, suggesting a role for these peptides in the pathogenesis and/or symptomatology of this condition. 7. Cardiopulmonary bypass, a model of activation of the contact system, activated both the plasma and tissue KKS. 8. Measurement of individual bradykinin and kallidin peptides and their metabolites gives important information about the operation of the plasma and tissue KKS and their role in physiology and disease states.