EFFECT OF KRN4884 ON LIPID-METABOLISM IN HYPERLIPIDEMIC RATS

1. KRN4884 is a novel pyridinecarboxamidine type potassium channel ope ner. 2. To determine whether KRN4884 affects lipid metabolism, we inve stigated its effects on serum lipid levels by using two types of hyper lipidemic rats: genetically hyperlipidemic obese Zucker rats and diet- induced hyperlipidemic rats fed a high fat diet. KRN4884 dose dependen tly decreased systolic blood pressure in Zucker rats. 3. Oral administ ration of KRN4884 (1-10 mg/(kg day) for 14 days dose dependently reduc ed serum triglyceride levels in Zucker rats. The reductions in serum t riglyceride were associated with reductions in triglyceride in chylomi cron and very low density lipoprotein. 4. KRN4884 produced no change i n serum insulin and glucose levels in Zucker rats. 5. KRN4884 exhibite d a similar triglyceride lowering effect in diet-induced hyperlipidemi c rats. 6. These results suggest that KRN4884 has a beneficial effect on serum triglyceride levels as well as a hypotensive effect. (C) 1998 Elsevier Science Inc.