Differential and interactive effects of calcium channel blockers and cholesterol content of the diet on jejunal uptake of lipids in rabbits

Abstract

The present study was undertaken to determine the effects of two classes of calcium channel blockers (CCB), nisoldipine (N) and verapamil (V), on the jejunal uptake of lipids in rabbits. The uptake of cholesterol and long-chain fatty acids into rabbit jejunum was examined after 6 and 36 min of exposure to N or V in vitro ("acute" studies), and after 3-wk feeding of N or V ("chronic" studies). Animals were fed either a low (0.08%) cholesterol diet (LCD) or a high (2.8%) cholesterol diet (HCD), with or without N or V added. Acute in vitro exposure of the jejunum to N or V did not affect the uptake of cholesterol or palmitic acid in rabbits fed LCD or HCD. The effect of N or V feeding depended upon the cholesterol content of the diet; adding N or V to LCD increased cholesterol uptake while adding N or V to HCD enhanced or lowered 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, whereas V lowered the uptake of stearic and linoleic acids and increased the uptake of oleic acid. These changes in lipid uptake were not due to variation in the animals' food intake, body weight gain, or intestinal mucosal surface area. The chronic administration of N or V results in an intestinal adaptative 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. (ABSTRACT TRUNCATED AT 250 WORDS)

Ion channels and transporters regulate nutrient absorption in health and disease

“…The application of different CCBs (nisoldipine and verapamil) in the jejunum of rabbits by D.A. Hyson et al showed different effects on various lipid component uptake, which correlated with the dietary proportion of cholesterol (Ch) 63 . Ka Ying Ma et al investigated that dietary Ca 2+ reduces plasma cholesterol by downregulating intestinal (NPC1L1) and MTTP, upregulating hepatic cholesterol‐7α‐hydroxylase (CYP7A1) and intestinal ABCG 5/8 64 .…”

“…Hyson et al showed different effects on various lipid component uptake, which correlated with the dietary proportion of cholesterol (Ch). 63 Ka Ying Ma et al investigated that dietary Ca 2+ reduces plasma cholesterol by downregulating intestinal (NPC1L1) and MTTP, upregulating hepatic cholesterol‐7α‐hydroxylase (CYP7A1) and intestinal ABCG 5/8. 64 Then, Gulsum E. Muku et al studied that NPC1L1 expression in the liver and intestine depends on sterol regulatory element binding protein 2 (SREBP‐2) activity, aryl hydrocarbon receptor (AHR) induces proteolytic degradation of mature SREBP‐2 (mSREBP2) in a Ca 2+ ‐dependent manner in Caco‐2 cells, which is associated with AHR ligand‐mediated upregulation of membrane Ca 2+ channels encoded by transient receptor potential cationic channel (TRPV6) gene.…”