Type 2 Bradykinin-Receptor Antagonism Does Not Modify Kinin or Angiotensin Peptide Levels

Abstract —Type 2 bradykinin (B 2 )-receptor antagonists have been used to define the role of endogenous kinin peptides. However, interpretation of the effects of B 2 -receptor antagonists has been limited by lack of information concerning the effects of these antagonists on endogenous kinin and angiotensin peptide levels. If kinin levels were subject to short-loop-feedback regulation mediated through B 2 receptors, then a reactive increase in kinin levels might blunt the effects of B 2 -receptor antagonism and stimulate type 1 bradykinin receptors. Moreover, kinins have been implicated in the control of renin secretion. We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B 2 receptor and whether endogenous kinins acting through the B 2 receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels. The B 2 -receptor antagonist icatibant (1 mg/kg) was administered to rats by intraperitoneal injection, and circulating and tissue levels of angiotensin and kinin peptides were measured after 4 hours. Icatibant produced 75% occupancy of B 2 receptors in the inner stripe of the renal medulla. Icatibant did not influence plasma levels of renin, angiotensinogen, angiotensin-converting enzyme, neutral endopeptidase, or circulating or tissue levels of angiotensin and bradykinin peptides. This study demonstrated that kinin levels are not subject to short-loop-feedback regulation mediated through B 2 receptors and that endogenous kinin levels acting through the B 2 receptor do not modulate the renin-angiotensin system.