Role of probucol on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy.

Abstract

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.

• Authors: Marie-Claude Aubin, Michel Carrier, Yan Fen Shi, Jean-Claude Tardif, Louis P Perrault
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 47 Issue 5 Pg. 702-10 (May 2006) ISSN: 0160-2446 [Print] United States
• PMID: 16775511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Lipid Peroxides
• Nitrates
• Nitrites
• Angiotensin II
• Serotonin
• Superoxide Dismutase
• Cyclic GMP
• Probucol
• Bradykinin

Topics

• Angiotensin II (blood)
• Animals
• Antioxidants (pharmacology)
• Bradykinin (pharmacology)
• Coronary Vessels (drug effects, metabolism, physiopathology)
• Cyclic GMP (analysis)
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Fibrosis (prevention & control)
• Hypertrophy, Left Ventricular (metabolism, pathology, physiopathology, prevention & control)
• In Vitro Techniques
• Lipid Peroxides (blood)
• Male
• Myocytes, Cardiac (pathology)
• Nitrates (blood)
• Nitrites (blood)
• Probucol (pharmacology)
• Serotonin (pharmacology)
• Superoxide Dismutase (metabolism)
• Swine
• Vasodilation (drug effects)