Peptidases modulate bradykinin-induced arteriolar dilation in the hamster cheek pouch.

The purpose of this study was to investigate whether angiotensin-converting enzyme (ACE; EC 3.4.15.1) and neutral endopeptidase (NEP; EC 3.4.24.11), two membrane-bound metalloenzymes that are widely distributed in the peripheral microcirculation and degrade kinins very effectively, modulate bradykinin-induced arteriolar dilation in vivo. Using intravital microscopy, we measured diameter of second-order arterioles in the hamster cheek pouch during suffusion of bradykinin (0.1-10.0 microM) before and after topical application of captopril (10.0 microM) and phosphoramidon (10.0 nM). We found that each inhibitor significantly potentiated bradykinin-induced increase in arteriolar diameter (P < 0.05). Suffusion of other proteinase inhibitors (excluding ACE and NEP inhibitors) had no significant effect on bradykinin-induced responses. Captopril and phosphoramidon did not potentiate isoproterenol (0.1 microM)-induced arteriolar dilation in the cheek pouch. Collectively, these data indicate that ACE and NEP each plays an important role in regulating bradykinin-induced vasorelaxation in the peripheral microcirculation in vivo.