Role of angiotensin II in injury-induced neointima formation in rats.
Angiotensin converting enzyme inhibition markedly suppresses neointima formation in response to balloon catheter-induced vascular injury of the rat carotid artery. To determine whether this effect was mediated through the vasoactive peptide angiotensin II (Ang II), two approaches were followed. First, the balloon model was used to compare the effects of continuous infusion of Ang II, with and without concurrent converting enzyme inhibition by cilazapril; second, the effects of the orally active nonpeptidic Ang II receptor antagonist DuP 753 were analyzed. Morphometric analysis was performed at 14 days after balloon injury. Animals that received continuous infusion of Ang II (0.3 micrograms/min/rat) were found to have significantly greater neointima formation in response to balloon injury than controls. Animals treated with cilazapril (10 mg/kg/day) had markedly reduced neointima formation, but in animals receiving infusion of Ang II, treatment with cilazapril did not suppress development of neointimal lesions. In the second group of experiments, DuP 753 (10 mg/kg twice daily) was as effective to prevent neointima formation as cilazapril. These data support the conclusions that converting enzyme inhibition prevents neointima formation after vascular injury through inhibition of Ang II generation.
Osterrieder
W
W
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Müller
R K
RK
Powell
J S
JS
Clozel
J P
JP
Hefti
F
F
Baumgartner
H R
HR
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D017315:Cilazapril; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D011724:Pyridazines; D013777:Tetrazoles; D000804:Angiotensin II; D017315:Cilazapril; D019808:Losartan