DIFFERENTIAL AND INTERACTIVE EFFECTS OF CALCIUM-CHANNEL BLOCKERS AND CHOLESTEROL CONTENT OF THE DIET ON JEJUNAL UPTAKE OF LIPIDS IN RABBITS

The present study was undertaken to determine the effects of two class es of calcium channel blockers (CCB), nisoldipine (N) and verapamil (V ), on the jejunal uptake of Lipids in rabbits. The uptake of cholester ol and longchain fatty acids into rabbit jejunum was examined after 6 and 36 min of exposure to N or V in vitro (''acute'' studies), and aft er 3-wk feeding of N or V (''chronic'' studies). Animals were fed eith er a low (0.08%) cholesterol diet (LCD) or a high (2.8%) cholesterol d iet (HCD), with or without N or V added. Acute in vitro exposure of th e jejunum to N or V did not affect the uptake of cholesterol or palmit ic acid in rabbits fed LCD or HCD. The effect of N or V feeding depend ed upon the cholesterol content of the diet; adding N or V to LCD incr eased cholesterol uptake while adding N or V to HCD enhanced or lowere d cholesterol uptake, respectively. Both N and V increased the uptake of stearic acid in LCD. N in HCD had no effect on fatty acid uptake, w hereas V lowered the uptake of stearic and linoleic acids and increase d the uptake of oleic acid. These changes in lipid uptake were not due to variation in the animals' food intake, body weight gain, or intest inal mucosal surface area. The chronic administration of N or V result s in an intestinal adaptive process that alters the jejunal uptake of lipids, the direction of which is influenced by the class of CCB, and by the cholesterol content of the diet. The serum lipid-lowering effec t of administering N to rabbits fed HCD demonstrated previously is unl ikely to be the result of a decrease in intestinal lipid uptake.