Atherosclerosis-inhibiting effect of an antibradykinin agent, pyridinolcarbamate

An antibradykinin and antilysylbradykinin agent, pyridinolcarbamate (2,6-bis-hydroxymethylpyridine- bis N- methylcarbamate), has a potent preventive effect on the edematous arterial reaction, and has been shown to possess an antiatherogenic property on the basis of the results obtained in the present series of experiments with 118 rabbits. The feeding of a high-cholesterol diet to the animals over a prolonged period of 13 to 15 weeks was employed to induce the experimental atherosclerosis, and the daily administration of pyridinolcarbamate in doses of 5 and 10 mg. per kilogram was shown to exert a powerful effect in preventing the apperance of atheromatous changes (p < 0.01) and the deposition of cholesterol in the aortic wall (p < 0.001), even under extremely high levels of serum cholesterol exceeding 2,000 mg. per deciliter. It also prevented the formation of atheroma, its fatty degeneration and necrosis, showing a fibrous healing and a striking regeneration of smooth muscles in the lesions. The antiatherogenic property of this compound is not related to an influence on the level of cholesterol in the blood; in fact, hypercholesterolemia is not depressed by the drug. The antiatherogenic property has been presumed to correlate possibly with the kinin-antagonistic effect of this compound.