Up-regulation of hepatic LDL receptor gene expression by monatepil, a novel calcium antagonist, in high cholesterol diet-fed Japanese monkeys.

Abstract

The action of the novel antihypertensive calcium antagonist monatepil on the hepatic LDL receptor was investigated at the gene expression level to clarify the mechanism of its hypolipidemic effect. In cholesterol-fed control monkeys, the LDL receptor mRNA level decreased to approximately 30% of that in the normal diet-fed monkeys. However, the administration of monatepil increased LDL receptor mRNA to normal levels (three- to fourfold stimulation). It is suggested that monatepil raises the number of LDL receptors in liver tissue and that this increase may accelerate the removal of plasma LDL. Treatment with prazosin, an alpha 1-adrenoceptor antagonist, also increased the LDL receptor mRNA level, but this restorative effect was much weaker than that of monatepil, suggesting that mechanisms additional to its alpha 1-adrenoceptor blocking activity are involved in the hypolipidemic effect of monatepil.