The role of a local angiotensin system in the vascular response to arterial injury was investigated by administering the angiotensin-converting enzyme (CE) inhibitor cilazapril to normotensive rats in which the left carotid artery was subjected to endothelial denudation and injury by balloon catheterization. In control animals, by 14 days after balloon injury, the processes of smooth muscle cell (SMC) proliferation, migration of SMCs from the media to the intima, and synthesis of extracellular matrix produced marked thickening of the intima, with reduction of the cross-sectional area of the lumen. However, in animals that received continuous treatment with the CE inhibitor, neointima formation was decreased (by about 80 percent), and lumen integrity was preserved. Thus, the angiotensin-converting enzyme may participate in modulating the proliferative response of the vascular wall after arterial injury, and inhibition of this enzyme may have therapeutic applications to prevent the proliferative lesions that occur after coronary angioplasty and vascular surgery.

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Exposure of type III collagen coats on plastic cover slips In parallel-plate perfuslon chambers to flowing nonanticoagulated human blood resulted In deposition of platelets and fibrin. Blood was drawn directly from an antecubltal vein by an occluslve roller pump over the collagen coats In chambers having flow silts of different dimensions, so that wall shear rates of 100,650, and 2600 s~1 were obtained at 10 ml/mln. Coagulation was minimally activated during the passage of blood from the vein to the chamber as shown by fibrlnopeptlde A levels of 3.7 ng/ml after 5-mlnute perfuslons. The surface coverage with platelets increased from 18% at 100 s" 1 to 59% at 2600 s \ and the corresponding thrombus volumes Increased from 2 to 22 fim'/fim', respectively. This contrasted with the coverage with fibrin on collagen, which decreased from 28% at 100 s 1 to 9% at 2600 s~1. Fibrin deposits on the thrombi covered 6% of the surface irrespective of the shear rate, Indicating that some of the deposited platelets accelerated the deposition of fibrin. The type III collagen preparation did not activate factor XII and did not possess tissue factor activity, Indicating that the surface Itself was not procoagulant However, a correlation between deposited leukocytes and surface coverage with fibrin was observed ( T he component of the vessel wall that most potently triggers the formation and growth of thrombi is considered to be collagen.1 -2 So far, 13 species of collagen have been identified, and many have been localized in the vessel wall.3 ' 4 One of these is type III collagen, which is synthesized by endothelial cells 6 and is present in subendothelium. Type III collagen binds platelets and builds up thrombi when exposed to flowing citrated blood. 87 Furthermore, in fibrillar form It triggers platelet aggregation when added to stirring platelet-rich plasma.8 However, controversy exists as to whether collagens are able to initiate coagulation through activation of coagulation factor XII 9 1 0 1 1 and thereby amplify its thrombogenic potential. Activation of factor XII leads to generation of thrombin and fibrin, which respectively reinforce growth and stability of thrombi.12 - 18From F. Hoffmann-La Roche Ltd, Pharma Research/CVD, Basle, Switzerland.Helene Sage is at the Department of Biological Structure, University of Washington, Seattle, Washington.Kjell S. Sakariassen's present address is at the Biotechnology Center of Oslo, Gausdalsallein 21, Post-box 1125, Bllndem 0316, University of Oslo, Oslo 3, Norway., Address for correspondence: Prof. Hans R. Baumgartner, F. Hoffmann-La Roche Ltd, Pharma Research/CVD, Qrenzacherstrasse 124, CH-4002 Basle, Switzerland. Received May 3,1989; revision accepted November 17,1989. The interactions between nonanticoagulated blood and type III collagen have not yet been studied. Since type III collagen is one of the most abundant collagens in subendothelium, 17 and as such may become exposed to blood at the sites of vascular injury, we decided to expose surfaces coated with fibrillar human t...

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