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 an giotensin I-converting enzyme overexpression in smooth muscle cells after v ascular injury. Rat carotid arteries isolated at days 2 to 14 after in vivo endothelial denudation were compared with the contralateral freshly denude d (control) vessels. Arterial rings were constricted ex vivo with angiotens in I in the absence or presence of the angiotensin I-converting enzyme inhi bitors captopril (300 nM and 3 mu M) 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. Contra ctions to angiotensin I were unaffected after injury. Inhibition by captopr il and perindoprilate of angiotensin I-induced contractions was significant ly less potent in injured arteries at day 7 as compared to control vessels. Mechanical removal of neointimal smooth muscle cells normalized the inhibi tion by captopril in injured arteries at day 7. Captopril did not affect an giotensin ii-induced contractions. Thus, upregulation of angiotensin I-conv erting enzyme after arterial injury confers resistance to angiotensin I-con verting enzyme inhibitors. (C) 2000 Elsevier Science B.V. All rights reserv ed.