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Influence of the acyl-coenzyme A:cholesterol--acyltransferase inhibitor octimibate on cholesterol transport in rat mesenteric lymph.

The effect of the new inhibitor of acyl-coenzyme A:cholesterol-acyltransferase, octimibate (sodium 8-[1,4,5-triphenyl-1H-imidazole-2yl)-oxy)octanoate), on the cholesterol transport in rat mesenteric lymph was evaluated. During intraduodenal infusion of a triglyceride-phospholipid emulsion, volume and triglyceride concentration of lymph collected from a mesenteric lymph fistula remained constant in control and treated rats. After addition of 3.75 mg 3H-cholesterol/h to the intraduodenal infusion, cholesterol content of lymph increased to about double the basic concentration in control rats. Yet there was no significant change of lymph cholesterol in treated animals, which had received 40 mg octimibate followed by ca. 120 mg/24 h x kg body weight octimibate added to the intraduodenal infusion. Up to 35% of the infused dose of 3H-cholesterol were recovered in lymph of control rats, in contrast to only 23% in lymph of treated rats. It is concluded that the inhibition of the intestinal acyl-coenzyme A:cholesterol-acyltransferase by octimibate may prevent the increase of cholesterol in mesenteric lymph induced by dietary cholesterol.