Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits.
In the present study, we compared the effect of atorvastatin (1 mg.kg(-1).day(-1)) and quinapril (0.5 mg.kg(-1).day(-1)) alone or in combination on inflammatory markers, endothelial function, intimal thickening and fibrinolytic balance in rabbits fed with either a control diet or a diet containing 1% (v/v) cholesterol for 12 weeks. Atorvastatin alone or in combination partially prevented the increase in cholesterol plasma levels observed in rabbits fed with the cholesterol-rich diet, but did not modify blood pressure levels. Quinapril administration did not alter any of these parameters in any group. Hypercholesterolaemia increased plasma levels of interleukin-1beta, interleukin-6, interferon-gamma and C-reactive protein, reduced acetylcholine-induced relaxation and produced intimal thickening. Likewise, atherosclerotic rabbits had reduced plasma tissue-type plasminogen activator activity and D-dimer levels and an increase in plasminogen-activator inhibitor-1 activity. Both drugs enhanced acetylcholine-induced relaxation, reduced intimal thickening and improved fibrinolytic balance in atherosclerotic rabbits in a similar manner. Their combination did not induce additive effects on these parameters. However, only the combination of both drugs was able to prevent the increase in inflammatory markers induced by hypercholesterolaemia. In summary, these data suggest that quinapril and atorvastatin had comparable beneficial effects on the alterations of vascular function and structure as well as fibrinolytic balance in atherosclerotic rabbits. In addition, the combination of atorvastatin and quinapril exerts a synergistic effect on inflammatory markers, which individual treatment, at the doses used, was not able to modify.
Oubiña
M Pilar
MP
Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain.
de las Heras
Natalia
N
Cediel
Eva
E
Sanz-Rosa
David
D
Aragoncillo
Paloma
P
Díaz
Cristina
C
Hernández
Gonzalo
G
Lahera
Vicente
V
Cachofeiro
Victoria
V
D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D000077583:Quinapril; D011817:Rabbits; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D017539:Tunica Intima / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects
D000214:Acyl Coenzyme A; D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D011758:Pyrroles; D044005:Tetrahydroisoquinolines; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000069059:Atorvastatin; D000077583:Quinapril