A HIGH CHOLESTEROL DIET BLOCKS THE EFFECT OF CALCIUM-CHANNEL BLOCKERSON THE UPTAKE OF SUGARS IN RABBIT INTESTINE

Two classes of calcium channel blockers, nisoldipine (NIS) and verapam il (VER), alter the intestinal uptake of sugars, and varying the lipid composition of the diet also modifies intestinal transport function. This study was undertaken in adult male New Zealand rabbits to assess the effect of 3 weeks of dosing with NIS (1 mg . kg(-1). day(-1)) or V ER (4 mg . kg(-1). day(-1)) on the in vitro jejunal uptake of D-galact ose and L- or D-glucose. The value of the maximal transport rate of D- galactose (V-max) increased with NIS and VER, compared with control ve hicle. The value of the apparent Michaelis constant (K-m) rose with NI S and fell with VER, and the value of the passive permeability coeffic ient (P-d) estimated from the uptake of L-glucose fell with NIS and ro se with VER. These effects of NIS and VER on V-max, K-m, and P-d were prevented by feeding a high cholesterol (2.8%) supplemented chow diet (HCD), as compared with chow alone. These effects were not due to any change in the animal's weight gain or intestinal mucosal surface area. The acute exposure of the jejunal tissue in vitro to varying concentr ations of NIS but not VER reduced the uptake of c-glucose but had no e ffect on basal short circuit current (I-sc) in either chow or HCD. I-s c stimulated with glucose or theophylline was less in chow-fed rabbits compared with HCD-fed rabbits given NIS or VER. Thus, the active tran sport of sugars by the sodium-dependent transporter in the brush-borde r membrane, SGLT1, and the passive uptake by the paracellular route ar e variably influenced by these two classes of calcium channel blockers , and this effect is modified by the cholesterol content of the diet.