Angiotensin-converting enzyme inhibitor versus angiotensin II, AT1 receptor antagonist. Effects on smooth muscle cell migration and proliferation after balloon catheter injury.
The angiotensin-converting enzyme (ACE) inhibitor, benazeprilat and the angiotensin II (Ang II), AT1-specific receptor antagonist, DuP753, were compared for their effects on intimal lesion formation as well as smooth muscle cell (SMC) proliferation and migration in Sprague Dawley rats after carotid balloon injury. Both the ACE inhibitor (benazeprilat, 3 mg/kg/day) and the AT1 antagonist (DuP 753, 10 mg/kg/day) significantly reduced intimal lesion formation after balloon injury (by 35% and 49%, respectively). Medial SMC proliferation after injury was reduced 53% by the AT1 antagonist; however, the ACE inhibitor had no effect on SMC proliferation. SMC migration was reduced 94% by the AT1 antagonist and 68% by the ACE inhibitor. These data demonstrate the importance of Ang II in SMC proliferation and migration after balloon injury. They also demonstrate that in the balloon injury model, the ACE inhibitor reduced intimal lesion size by inhibiting SMC migration alone without affecting SMC proliferation. A more pronounced reduction in lesion size was obtained after AT1 antagonism, however, when both SMC migration and proliferation were inhibited.
Prescott
M F
MF
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
Webb
R L
RL
Reidy
M A
MA
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan; C052133:benazeprilat