Intestinal Brush Border Calcium Uptake in Spontaneously Hypertensive Rats and Their Genetically Matched WKY Rats

Abstract

The current studies were designed to characterize calcium transport by intestinal brush border membrane in the spontaneously hypertensive rat (SHR) and normotensive control, the Wistar-Kyoto (WKY) rat. The biochemical and functional purity of the intestinal brush border membranes in SHR and WKY rats was validated by marker enzymes and the ability to transiently transport D-glucose in the presence of Na+ gradient. Calcium transport into duodenal and jejunal vesicles represented a minor binding component and transmembrane movement as evident by initial rate studies, A23187 studies, and lanthanum displacement experiments. Initial rate and time course of calcium uptake was lower in SHR compared with WKY rats. Kinetic analysis of calcium uptake by the jejunum (total uptake minus binding component) showed a Vmax of 6.98 +/- 0.2 and 1.8 +/- 0.2 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.001), whereas Km values were 0.76 +/- 0.04 and 0.87 +/- 0.1 mM for WKY rats and SHR, respectively. Similar kinetic analysis of calcium uptake by the duodenal segments showed a Vmax of 10.3 +/- 0.8 and 2.8 +/- 0.2 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.01). Km values were 0.7 +/- 0.2 and 0.3 +/- 0.06 mM (P greater than 0.05). Vmax of calcium uptake in the 2-week-old rats (prehypertensive period) was 6.0 +/- 0.3 and 3.53 +/- 0.3 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.001), whereas Km values were 0.60 +/- 0.07 and 0.5 +/- 0.01 mM, respectively. These results suggest that calcium binding and uptake by duodenal and jejunal intestinal brush border membranes of SHR is significantly decreased compared with WKY rats. The decrease in transmembrane calcium uptake is secondary to decrease in Vmax and is present before the appearance of hypertension, implying a genetically determined defect in calcium uptake in intestinal brush border membranes of the SHR.

Magnesium Uptake by Intestinal Brush-Border Membranes of Spontaneously Hypertensive Rats

“…In contrast, Ca2+ uptakes by both duodenal and jejunal BBM are significantly lower in SHR in comparison to WKY rats (12,13). A defect in intestinal vitamin Ddependent calbindin-Dgk ( 16) and in alkaline phosphatase ( 14-16, 2 1) recorded in SHR has been associated with Ca2+ malabsorption.…”

“…But in the case of Ca2+, the kinetic study suggests one single mediated component with different characteristics in the two types of rats (13).…”

“…However, a reduced uptake of Ca2+ by duodenal mucosa (1 l), by isolated duodenal enterocytes (8), and by duodenal and jejunal brush-border membranes of SHR ( 12,13), together with an impaired Ca2+ extrusion via the Ca2+/ Na+ exchanger by jejunal basolateral membranes, has been evidenced in SHR, the ATP-dependent pump being unaffected (10). A lower intracellular Ca2+ concentration found in duodenal cells of young SHR (8) and in jejunal cells of adult SHR (14) also points to an alteration of Ca2+ handling by the SHR intestine.…”