Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist.

1. The effect of icatibant (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin) a potent B2-kinin receptor antagonist, was studied on bradykinin-induced vasodilation in the human forearm. 2. Eight healthy normotensive men were studied in a rising dose random-placebo controlled study. Placebo and icatibant (20, 50 and 100 micrograms kg-1 i.v.) were administered double-blind. Forearm blood flow was measured by venous occlusion plethysmography during rising dose brachial artery infusions of bradykinin (10-3,000 ng min-1) 60-90 min after placebo or icatibant. 3. Plasma concentrations of icatibant fell exponentially following each of three doses, up to the final measurement. Elimination half-lives calculated from linear regression of the mean data were 25, 27 and 29 min after 20, 50 and 100 micrograms kg-1 doses respectively. 4. Icatibant inhibited the effect of bradykinin (P < 0.001 at each dose of icatibant) in a dose-dependent manner. Bradykinin (100 ng min-1) increased mean blood flow in the infused arm by 238 +/- 31% when infused following placebo, by 112 +/- 21% after icatibant 20 micrograms kg-1, by 71 +/- 14% after icatibant 50 micrograms kg-1 and by 48 +/- 9% after icatibant 100 micrograms kg-1. 5. These results demonstrate that icatibant antagonises B2-receptor mediated vasodilation in human forearm resistance vessels. The findings provide a quantitative basis for future studies of the role of bradykinin in the response to angiotensin converting enzyme inhibitors and in circulatory disease.