Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits.
The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, 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 daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels 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 animals). An antioxidant mechanism is unlikely to explain this data, since 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.
Hernandez
A
A
Institute of Pharmacological Sciences, Center for Cardiopulmonary Pharmacology, University of Milan, Italy.
Barberi
L
L
Ballerio
R
R
Testini
A
A
Ferioli
R
R
Bolla
M
M
Natali
M
M
Folco
G
G
Catapano
A L
AL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D007189:Indans; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D002784:Cholesterol; D002216:Captopril; D005996:Nitroglycerin; C047759:delapril; D009638:Norepinephrine