The lipid-lowering agent probucol may be efficacious, through its antioxidant properties, to limit and reverse the vascular endothelial dysfunction associated with left ventricular hypertrophy (LVH). LVH was induced by performing an aortic banding (AB) on swine, except for controls (group 1). The untreated AB group received a placebo (group 2) whereas the treated groups received probucol (1000 mg/d orally); the third group began its treatment on the day of the banding (for 60 d), the fourth began on day 30 and the fifth on day 60 after AB (both for 30 d). Hypertrophy was assessed by echocardiography and histology. Coronary vascular reactivity was evaluated in organ chambers and endothelial function by quantification of NO2−/NO3− and cyclic guanosine-3′,5′-monophosphate. To assess oxidative stress, hydroperoxides and angiotensin II levels as well as superoxide dismutase activity were evaluated. After treatment with probucol, a significant decrease in left ventricle/body weight ratio was observed compared with the untreated group. Dose-response curves of the probucol groups showed an improvement in endothelium-dependent relaxations, associated with increased nitric oxide bioavailability and decreased angiotensin II and hydroperoxide levels. In conclusion, the antioxidant probucol limited the development and induced the regression of LVH and the associated coronary endothelial dysfunction.
Departments of †Pharmacology
§Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
Reprints: Louis P. Perrault, MD, PhD, Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8 (e-mail: firstname.lastname@example.org)
Received for publication January 30, 2006; accepted April 13, 2006
This work was supported by the “Fondation de l'Institut de Cardiologie de Montréal (FICM)”, the Department of Surgery of the Université de Montréal. Dr Louis P. Perrault is a Research Scholar from the “Fonds de la recherche en santé du Québec (FRSQ)”. Dr Jean-Claude Tardif holds the Pfizer and Canadian Institutes of Health Research Chair in Atherosclerosis.