Oral administration of NO synthase inhibitor failed to promote arteriosclerotic lesions in the aorta and the coronary arteries of rabbits fed cholesterol

Abstract

We examined whether or not the oral administration of l-nitroarginine methylester ( l-NAME), an inhibitor of nitric oxide (NO) synthase, promotes cholesterol-induced arteriosclerosis in the aorta and the coronary artery. Thirty-six male Japanese white rabbits were fed 0.5% cholesterol-containing laboratory chow and randomly assigned to the following three groups: (1) water, (2) 80 μg/ml l-NAME and (3) 400 μg/ml l-NAME in drinking water. The rabbits were fed a 0.5% cholesterol-containing diet for 8 months. During the 8-month period, the concentration of total cholesterol and l-nitroarginine in the serum and the mean blood pressure were measured. The concentration of NO 3 in the serum was also measured. After sacrifice, the aortic surface involvement (AI%), the ratio of the thickened intima to the media and the contents of the total cholesterol of the aorta, the maximum % stenosis of the subepicardial large coronary artery, the % frequency of the nearly completely occlusive distal small coronary artery and the area of the myocardial fibrosis were all measured. We found no statistical difference among the three groups regarding the degree of arteriosclerotic lesions of the aorta and of the large coronary artery, and the area of myocardial fibrosis, as well as the serum cholesterol exposure index (the area under the curve of the serum total cholesterol concentration) and the mean blood pressure. However, the serum concentration of l-nitroarginine was approximately 50 and 200 μM/l in groups 2 and 3, respectively. The concentration of NO 3 in the serum in group 1 was significantly higher than that in groups 2 and 3. We thus conclude, that the oral administration of l-NAME in the rabbits fed a cholesterol-containing diet for 8 months failed to promote arteriosclerotic lesions in the aorta and the coronary artery, even though the serum concentration of l-nitroarginine increased sufficiently to inhibit NO synthase in the arterial endothelium and the NO 3 concentration in the serum decreased in the rabbits given l-NAME.