Intestinal calcium transport in spontaneously hypertensive rats and their genetically matched wistar–kyoto rats

The present study was designed to investigate calcium uptake by the intestinal endoplasmic reticulum in the spontaneously hypertensive rat (SHR) and its genetically matched normotensive control, the Wistar–Kyoto rat (WKY). The calcium uptake was characterized before (weanling) and after (adult) development of hypertension in SHR and their age-matched WKY controls. Adenosine 5′-triphosphate (ATP)-driven calcium uptake with time was stimulated several-fold compared with the no-ATP condition, and the maximal uptake occurred after 15 min in both SHR and WKY. The maximal ATP-dependent calcium uptake was significantly greater in the intestinal endoplasmic reticulum of adult SHR than in that of WKY (P < 0.05). The initial rate of calcium uptake was linear up to 30 s in both SHR and WKY. The kinetics of ATP-dependent calcium uptake at a concentration between 0.1 and 1.0µmol/l showed a maximal uptake (V_max) of 1.89 ± 0.3 and 1.06 ± 0.1 nmol/mg protein per 15 s for adult SHR and WKY, respectively (P < 0.02), and binding constant (K_m) values of 0.15 ± 0.08 and 0.12 ± 0.05 µmol/l, respectively. The ontogeny of calcium uptake by intestinal endoplasmic reticulum was characterized before the development of hypertension in weanling (3-week-old) SHR and WKY. In both SHR and WKY weanlings, calcium uptake by the intestinal endoplasmic reticulum was enhanced several-fold by the presence of ATP compared with the no-ATP condition, and the maximal uptake occurred after 15 min. The maximal ATP-dependent calcium uptake was significantly greater in 3-week-old SHR than in age-matched WKY (P < 0.05). Kinetic analysis of the ATP-dependent calcium uptake showed a V_max of 0.8 ± 0.08 and 0.38 ± 0.06 nmol/mg protein per 15 s for weanling SHR and WKY, respectively (P < 0.01), and K_m values of 0.11 ± 0.04 and 0.18 ± 0.09µmol/l, respectively. These results suggest that SHR exhibit abnormalities in intracellular calcium handling and that these changes are present before the appearance of hypertension.