Type 2 bradykinin-receptor antagonism does not modify kinin or angiotensinpeptide levels

Type 2 bradykinin (B-2)-receptor antagonists have been used to define the r ole of endogenous kinin peptides. However, interpretation of the effects of B-2-receptor antagonists has been limited by lack of information concernin g the effects of these antagonists on endogenous kinin and angiotensin pept ide levels. If kinin levels were subject to short-loop-feedback regulation mediated through B-2 receptors, then a reactive increase in kinin levels mi ght blunt the effects of B-2-receptor antagonism and stimulate type 1 brady kinin receptors. Moreover, kinins have been implicated in the control of re nin 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 le vels and circulating and tissue angiotensin peptide levels. The B-2-recepto r antagonist icatibant (I mg/kg) was administered to rats by intraperitonea l injection, and circulating and tissue levels of angiotensin and kinin pep tides were measured after 4 hours. Icatibant produced 75% occupancy of B-2 receptors in the inner stripe of the renal medulla. Icatibant did not influ ence 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 sub ject to short-loop-feedback regulation mediated through B-2 receptors and t hat endogenous kinin levels acting through the B-2 receptor do not modulate the renin-angiotensin system.