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.
Gao
X P
XP
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-4575.
Anding
P
P
Robbins
R A
RA
Rennard
S I
SI
Rubinstein
I
I
D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000008:administration & dosage; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004338:Drug Combinations; D010450:Endopeptidases / Q000502:physiology*; D006020:Glycopeptides / Q000008:administration & dosage; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D011480:Protease Inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004338:Drug Combinations; D006020:Glycopeptides; D011480:Protease Inhibitors; D002216:Captopril; D010450:Endopeptidases; D007545:Isoproterenol; D001920:Bradykinin; C008890:phosphoramidon