Hypercholesterolemia in the course of chronic renal failure (CRF) is a significant risk factor for cardiovascular complications. It has been found that experimental CRF is associated with increased liver SREBP-2 mRNA level as well as in mature SREBP-2 protein abundance. This is probably the cause for increase in HMG-CoA reductase gene expression and, consequently, for increase in liver cholesterol synthesis and hypercholesterolemia in CRF rats. Surprisingly, enhanced liver cholesterologenesis in CRF rats occured even though cholesterol concentration in plasma and hepatocytes is increased, pointing to the hypothesis, that the physiological feedback inhibition of cholesterol synthesis may be disturbed in CRF rats. Therefore it was interesting to know if the dietary cholesterol exerts its inhibitory effect on the liver cholesterologenesis in the CRF rats. Control and CRF rats (achieved by 5/6 nephrectomy model) were kept on the normal or 1% cholesterol rich diet. After three days of cholesterol rich diet feeding, animals were killed under light ether anesthesia. It has been found that cholesterologenesis in the course of CRF, is inhibited by exogenous alimentary cholesterol. HMG-CoA reductase activity and HMG-CoA reductase mRNA level decreased significantly in the liver of control and CRF animals keep on the cholesterol enriched diet. The changes in cholesterol synthesis, HMG-CoA activity and HMG-CoA mRNA abundance were strictly associated with changes in SREBP-2 mRNA and mature SREBP level. Obtained results suggest that cholesterol enriched diet exerts similar effect on cholesterol synthesis in control and CRF rats.

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