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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:885.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Hypercholesterolemia and Hypertension Have Synergistic Deleterious Effects on Coronary Endothelial Function

Martin Rodriguez-Porcel; Lilach O. Lerman; Joerg Herrmann; Tatsuya Sawamura; Claudio Napoli; Amir Lerman

From the Department of Internal Medicine, Divisions of Cardiovascular Diseases (M.R.-P., J.H., A.L.) and Hypertension (L.O.L.), Mayo Clinic, Rochester, Minn; the National Cardiovascular Center Research Institute Fujishirodai (T.S.), Suita, Osaka, Japan; and the Department of Medicine (C.N.), University of Naples, Naples, Italy.

Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu

Objective— Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function.

Methods and Results— Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity.

Conclusions— These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

Key Words: animal models • coronary circulation • oxidant stress • risk factors

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