Angiotensin I-converting enzyme activity and vascular sensitivity to angiotensin I in rat injured carotid artery.
We used a vasoreactivity assay to examine the functional significance of angiotensin I-converting enzyme overexpression in smooth muscle cells after vascular injury. Rat carotid arteries isolated at days 2 to 14 after in vivo endothelial denudation were compared with the contralateral freshly denuded (control) vessels. Arterial rings were constricted ex vivo with angiotensin I in the absence or presence of the angiotensin I-converting enzyme inhibitors captopril (300 nM and 3 microM) or perindoprilate (1 nM). Angiotensin I-converting enzyme activity was determined by cleavage of the chromogenic substrate Hip-His-Leu. Angiotensin I-converting enzyme activity in injured arteries was increased (2-fold) at day 7 only after vascular injury. Contractions to angiotensin I were unaffected after injury. Inhibition by captopril and perindoprilate of angiotensin I-induced contractions was significantly less potent in injured arteries at day 7 as compared to control vessels. Mechanical removal of neointimal smooth muscle cells normalized the inhibition by captopril in injured arteries at day 7. Captopril did not affect angiotensin II-induced contractions. Thus, upregulation of angiotensin I-converting enzyme after arterial injury confers resistance to angiotensin I-converting enzyme inhibitors.
Lemay
J
J
Department of Pharmacology, Laboratory of Pharmacology of Vascular Pathologies, Centre de Recherche du C.H.U.M., Université de Montréal, 3840 St. Urbain Street., 7-133B, Montréal, Québec, Canada.
Hou
Y
Y
Tremblay
J
J
deBlois
D
D
D000800:Angioplasty, Balloon; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A