Response of spontaneously hypertensive rats to 1,25(OH)₂D₃ in vivo

Calcium absorption in spontaneously hypertensive rats (SHR) has been reported to be increased, decreased or not different from their normotensive Wistar Kyoto (WKy) control. One postulated reason for these conflicting results is an abnormal sensitivity to the intestinal effects of 1,25(OH)₂D₃ (1,25D₃). Previous studies in everted duodenal sacs and perfused duodenum examined the acute response to 1,25D₃ only in 12-week-old SHR, which however already had higher basal rates of calcium absorption. Inability to stimulate Ca absorption further was an unexcluded possibility. To test this hypothesis more vigorously, balance and in situ duodenal ⁴⁵Ca uptake studies were performed in SHY and WKy using four separate protocols yielding the following results. First, in response to pharmacological doses of 1,25D₃ (25 ng/100 g body wt/day x 3), four-week-old normotensive female SHR had higher net calcium absorption (41.4 vs. 31.1 mg/day; 61.6 vs. 48.1%), similar to the increases seen in the untreated state. These results suggest intrinsic epithelial differences independent of 1.25D₃. Ca absorption was similarly higher in 1,25D₃ treated male SHR (42.9 vs. 36.7 mg/day; 60.1 vs. 53.7%). Second, at 12 to 14 weeks of age, low doses of 1,25D₃ (8 ng/100 g body wt/day x 6) stimulated net Ca absorption in the female SHR (33.0 to 39.1 mg/day), but not in WKy (26.8 to 29.3 mg/day). In the male, positive effects were again seen only in the SHR (25 to 45 mg/day). Third, in response to three weeks of dietary Ca deprivation, in situ duodenal ⁴⁵Ca uptake, measured in the conscious wake state, was higher in 35-week-old SHR (70.9 vs. 53.0%). Fourth, prior parathyroidectomy did not abolish the accentuated response in duodenal ⁴⁵Ca uptake by 1,25D₃ treated SHR (85.4 vs. 69.4%). These data indicate in vivo hypersensitivity to 1,25D₃ in the SHR, independent of hypertension and consistent with the postulate of intrinsic epithelial transport abnormalities.