Untersuchungen über den Mechanismus der hypocholesterinämischen Wirkung der Nicotinsäure

Summary

The effects of intravenous injection of nicotinic acid (NA) on serum cholesterol were investigated in dogs and rabbits. The serum cholesterol was estimated simultaneously by two methods. 1. by the direct method ofZlatkis et al. and 2. by precipitation of the serum proteins with aceton-ethanol and subsequent estimation of cholesterol in the filtrate according to the method ofZak et al. The following results were obtained:

• 1. In cholesterol fed dogs and rabbits intravenous injection of NA (50–100 mg/kg) led to a sharp and significant drop of serum cholesterol, estimated by the aceton-ethanol method, whereas the serum cholesterol values estimated by the direct method were not influenced at the same time.

• 2. Heparin given 5 hours after NA injection raised again the lowered aceton-ethanol extractible serum cholesterol.

• 3. In rabbits with high cholesterol diet 130–350 mg trypanblue produced a considerable rise of serum cholesterol from 400–500 mg% to 1000–1200 mg% estimated by both methods. The effect of NA and Heparin on the serum cholesterol was abolished after trypanblue and normal actions of the two substances could not be observed before 3 weeks. Within this time the raised serum cholesterol decreased slowly.

• 4. Prolonged administration of NA (100 nig/kg s.c. 3 times a day) on rabbits with high cholesterol diet had no influence on the serum cholesterol estimated by the direct method. A transient fall of the serum cholesterol level was observed with the extraction method. Hypercholesterolemia and severe pathological lesions could not be prevented by the chronical NA administration.

• 5. The results were interpreted on the basis of a stimulating action of NA on the cells of the reticular endothelial system leading to an increased incorporation of lipid soluted cholesterol into lipoprotein molecules.