Intestinal Calcium Transport in Spontaneously Hypertensive Rats (SHR) and Their Genetically Matched WKY Rats

Abstract

Calcium transport across the basolateral membranes of the enterocyte represents the active step in calcium translocation. This step occurs by two mechanisms, an ATP-dependent pump and a Ca²⁺/Na⁺ exchange process. These studies were designed to investigate these two processes in jejunal basolateral membrane vesicles (BLMV) of the spontaneously hypertensive rats (SHR) and their genetically matched controls, Wistar-Kyoto (WKY) rats.

The ATP-dependent calcium uptake was stimulated several-fold compared with no ATP condition in both SHR and WKY, but no differences were noted between rate of calcium uptake in SHR and WKY. Kinetics of ATP-dependent calcium uptake at concentrations between 0.01 and 1.0 μM revealed a V _max of 0.67 ± 0.03 nmol/mg protein/20 sec and a K_m of 0.2 ± 0.03 μM in SHR and V _max of 0.69 ± 0.12 and a K_m of 0.32 ± 0.14 μM in WKY rats.

Ca²⁺/Na⁺ exchange in jejunal BLMV of SHR and WKY was investigated in two ways. First, sodium was added to the incubation medium (cis-Na⁺). Second, Ca²⁺ efflux from BLMV was studied in the presence of extravesicular Na⁺ (trans-Na⁺). Both studies suggest a decreased exchange of calcium and Na⁺. Kinetic parameters of Na⁺-dependent Ca²⁺ uptake at concentrations between 0.01 and 1.0 μM exhibited V _max of 0.05 ± 0.01 nanmol/mg protein/5 sec and a K_m of 0.21 ± 0.13 μM in SHR and V _max of 0.11 ± 0.02 nanmol/mg protein/5 sec and a K_m of 0.09 ± 0.05 in WKY, respectively. These results confirm that the intestinal BLMV of SHR and WKY rats have two mechanisms for calcium extrusion, an ATP-dependent Ca²⁺ transport process and a Na⁺/Ca²⁺ exchange process. The ATP-dependent process appears to be functional in SHR; however, the Ca²⁺/Na⁺ exchange mechanism appears to have a marked decrease in its maximal capacity. These findings suggest that calcium extrusion via Ca²⁺/Na⁺ is impaired in the SHR, which may lead to an increase in intracellular calcium concentration. These findings may have relevance to the development of hypertension.