Effect of KRN4884 on lipid metabolism in hyperlipidemic rats

1. KRN4884 is a novel pyridinecarboxamidine type potassium channel opener. 2. To determine whether KRN4884 affects lipid metabolism, we investigated its effects on serum lipid levels by using two types of hyperlipidemic rats: genetically hyperlipidemic obese Zucker rats and diet-induced hyperlipidemic rats fed a high fat diet. KRN4884 dose dependently decreased systolic blood pressure in Zucker rats. 3. Oral administration of KRN4884 (1-10 mg/(kg day) for 14 days dose dependently reduced serum triglyceride levels in Zucker rats. The reductions in serum triglyceride were associated with reductions in triglyceride in chylomicron and very low density lipoprotein. 4. KRN4884 produced no change in serum insulin and glucose levels in Zucker rats. 5. KRN4884 exhibited a similar triglyceride lowering effect in diet-induced hyperlipidemic rats. 6. These results suggest that KRN4884 has a beneficial effect on serum triglyceride levels as well as a hypotensive effect.