DELAPRIL SLOWS THE PROGRESSION OF ATHEROSCLEROSIS AND MAINTAINS ENDOTHELIAL FUNCTION IN CHOLESTEROL-FED RABBITS

The renin-angiotensin system is an important modulator of arterial blo od pressure and inhibitors of the angiotensin-converting enzyme (ACE-I s) and are currently used in the treatment of hypertension. The pleiot ropic actions exerted by angiotensin II (AngII) on the functionality o f the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an ant ioxidant effect has been attributed to thiol-containing ACE-Is, like C aptopril. The present study has been undertaken to investigate the eff ect of Delapril, a lipophilic ACE-I, on the development of atheroscler osis in cholesterol-fed rabbits. While it did not correct hyperlipidem ia, Delapril dose-dependently inhibited the development of atheroscler osis, expressed as aortic area covered by lesions (23.3 +/- 4.1, 21.3 +/- 2.4 and 18.5 +/- 3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2% +/- 6.4 for control animals) and its effect was similar to that of Captopril (14.5 +/- 5.1% at the dai ly dose of 25 mg/kg). Furthermore, Delapril partially and dose-depende ntly restored endothelium-dependent relaxation, which is impaired in v essels from hypercholesterolemic animals (51.80 +/- 12.18, 59.74 +/- 5 .16, 69.13 +/- 8.70 maximal percent relaxation versus 48.26 +/- 3.05% for the untreated control and 67.67 +/- 6.72% for Captopril-treated an imals). An antioxidant mechanism is unlikely to explain this data, sin ce Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases. (C) 1998 Els evier Science Ireland Ltd. All rights reserved.