Potentiation of the biological efficacy of bradykinin by ACE inhibitors: A shift in the affinity of the B-2 receptor?

We have recently demonstrated that the angiotensin I-converting enzyme (ACE) inhibitor ramiprilat augments the endothelium-dependent dilator response to bradykinin in the isolated perfused rat heart by an interaction at the B-2 receptor level. We have now investigated whether this is an effect of the ACE inhibitor class of compounds by studying the bradykinin-induced vasoconstriction in isolated segments of the rabbit jugular vein. Among five different ACE inhibitors, moexiprilat and ramiprilat proved to be the most effective in potentiating the constrictor response to bradykinin. This effect was not mimicked by other protease inhibitors or the synthetic ACE substrate hippuryl-L-histidyl-L-leucine. The ACE inhibitors, on the other hand, failed to affect the constrictor or dilator responses elicited by other receptor-dependent agonists in this vascular model. These findings demonstrate that ACE inhibitors selectively potentiate the B-2 receptor-mediated constrictor response to bradykinin in the rabbit jugular vein, possibly by increasing the affinity of the B-2 receptor.