EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ON INTIMAL THICKENING IN RABBIT COLLARED CAROTID-ARTERY

The positioning of a nonocclusive silicone collar around the rabbit ca rotid artery results in the formation of a neointima under a morpholog ically continuous endothelium. We wished to determine whether oral tre atment with angiotensin-converting enzyme (ACE) inhibitors prevents or retards intimal thickening and whether this is related to the blood p ressure (BP) lowering effects of such drugs. Silicone collars were pla ced around the left carotid artery of 104 male New Zealand white rabbi ts for 14 days. The contralateral carotid artery was sham-operated. Th ree ACE inhibitors were administered from 7 days before collar placeme nt until the end of the experiment: zabicipril(0, 0.03, 0.10, or 0.30 mg/kg/day), moexipril (0, 0.3, 1, or 3 mg/kg twice daily, b.i.d.), and enalapril (0 or 3 mg/kg/day). Each group consisted of 6-12 animals. B P and plasma ACE activity were measured in the nonanesthetized rabbits after 3-week treatment. To evaluate intimal thickening, we measured t he cross-sectional area of intima and media. The positioning of the co llar led to significant intimal thickening after 14 days. Although the ACE inhibitors decreased BP (zabicipril, 9, 16, 16%; moexipril, 10, 2 2, 31%; enalapril, 15%) and plasma ACE activity (zabicipril, 87, 88, 9 2%; moexipril, 79, 92, 93%; enalapril, 88%) significantly and dose dep endently, they did not reduce intimal thickening or the cross-sectiona l area of the media. Angiotensin II does not play a dominant role in c ollar-induced intimal thickening in rabbits. Furthermore, reducing the BP of normotensive rabbits does not alter neointima formation in this model.