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

Abstract

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 SHR 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 awake state, was higher in 35-week-old SHR (70.9 vs. 53.0%).(ABSTRACT TRUNCATED AT 250 WORDS)