Glunicate (LG 13979) protects the arterial wall from cholesterol-induced atherosclerotic changes in the rabbit without affecting plasma lipids

Glunicate is evaluated compared to nicotinic acid for effects on aortic atheromatous lesions, lipid parameters and factors involved in thrombosis and haemostasis in rabbits kept on a high-cholesterol diet for 12 weeks, using 2 doses of glunicate (0.17 and 0.69 g/day) and 1 of nicotinic acid (0.6 g/day). Glunicate afforded dose-dependent protection of the arterial wall from atheromatous lesions and from cholesterol and collagen accumulation, while nicotinic acid hardly had any effect. These effects were completely independent of plasma lipid-lowering action, the plasma levels of all lipids being indistinguishable in all cholesterol-fed groups. In addition to inducing the expected changes in the lipid pattern, the atherogenic diet increased platelet aggregation in response to collagen but not to ADP, prolonged the APTT and lowered the plasma fibrinogen levels. Both glunicate and nicotinic acid counteracted the effects of the diet on platelet aggregation and on APTT, but only glunicate normalised the fibrinogen levels. There was no change in PT or in prostacyclin-like activity release from the mesenteric artery after the diet or diet plus drugs.