Angiotensin converting enzyme protects acetylcholine-induced relaxation from its attenuation by formyl-methionyl-leucyl-phenylalanine in rat aorta.
OBJECTIVE
A chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine (fMLP) attenuated acetylcholine (ACh)-induced relaxation. Because angiotensin converting enzyme (ACE), which inactivates fMLP, is rich in vascular endothelial cells, we examined whether endothelial cell ACE inhibits the attenuating effect of fMLP on ACh-induced relaxation.


METHODS
ACh-induced relaxation was evaluated in aortic rings from 9-week-old Sprague-Dawley rats. We examined the effects of ACE, the ACE inhibitor captopril and/or fMLP on ACh-induced relaxation in aortas from rats with or without dexamethasone treatment, which enhances ACE activity.


RESULTS
Pre-treatment with ACE did not alter ACh-induced relaxation in control aortas but abolished the inhibitory effect of fMLP on ACh-induced relaxation [maximal relaxation (Emax): 95.4 +/- 1.2 versus 75.5 +/- 1.9%, P < 0.05]. Conversely, captopril enhanced the attenuation of ACh-induced relaxation by fMLP (Emax: 62.5 +/- 3.3 versus 74.0 +/- 2.2%, P < 0.05), although captopril did not affect ACh-induced relaxation in control aortas. In addition, fMLP did not attenuate ACh-induced relaxation in aortas from dexamethasone-treated rats (Emax: 89.7 +/- 3.7 versus 85.2 +/- 3.8%, NS), which enhanced ACE activity of aortas (3.37 +/- 0.25 versus 2.70 +/- 0.20 IU/mg protein, P < 0.05).


CONCLUSIONS
Endothelial-cell ACE attenuates the effect of fMLP on ACh-induced relaxation, possibly by its cleavage.
Ando
K
K
Department of Endocrinology and Nephrology, Faculty of Medicine, University of Tokyo, Japan. katsua-tky@umin.ac.jp
Fujita
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D000109:Acetylcholine