Response of spontaneously hypertensive rats to 1,25(OH)2D3 in vivo.
Response of spontaneously hypertensive rats to 1,25(OH)2D3 in vivo.
复制标题
自发性高血压大鼠体内对 1,25(OH)2D3 的反应。
DOI：
10.1038/ki.1986.213
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发表时间：
1986
影响因子：
19.6
通讯作者：
Lau,K
中科院分区：
文献类型：
--
作者：
Gafter,U;Eby,B;Martin,C;Lau,K
自发性高血压大鼠体内对 1,25(OH)2D3 的反应。据报道，自发性高血压大鼠 (SHR) 的钙吸收与正常血压 Wistar京都 (WKy) 对照组相比有所增加、减少或没有差异。这些相互矛盾的结果的一个推测原因是对 1,25(OH)2D3(1,25D3) 肠道效应的异常敏感性。先前对外翻十二指肠囊和灌注十二指肠的研究仅检查了 12 周龄 SHR 对 1,25D3 的急性反应，但其基础钙吸收率已经较高。无法进一步刺激钙吸收是一种不排除的可能性。为了更有力地检验这一假设，在 SHR 和 WKy 中使用四个单独的方案进行了平衡和原位十二指肠 45Ca 摄取研究，产生了以下结果。首先，响应药理剂量 1,25D3（25 ng/100 g 体重/天 × 3），四周龄血压正常的雌性 SHR 具有更高的净钙吸收（41.4 vs. 31.1 mg/天；61.6 vs. 48.1%），与未治疗状态下观察到的增加相似。这些结果表明内在上皮差异与 1,25D3 无关。 1,25D3 治疗的雄性 SHR 的钙吸收同样较高（42.9 毫克/天 vs. 36.7 毫克/天；60.1% vs. 53.7%）。其次，在 12 至 14 周龄时，低剂量 1,25D3（8 ng/100 g 体重/天 × 6）刺激雌性 SHR 的净 Ca 吸收（33.0 至 39.1 毫克/天），但不刺激 WKy（26.8 至 29.3 毫克/天）。在男性中，仅在 SHR（25 至 45 毫克/天）中再次观察到积极效果。第三，对于三周膳食钙缺乏的反应，在清醒状态下测量的原位十二指肠 45Ca 摄取在 35 周龄 SHR 中更高（70.9% vs. 53.0%）。第四，先前的甲状旁腺切除术并没有消除 1,25D3 治疗的 SHR 对十二指肠 45Ca 摄取的增强反应（85.4% vs. 69.4%）。这些数据表明 SHR 中对 1,25D3 的体内超敏反应，与高血压无关，并且与内在上皮转运异常的假设一致。
Response of spontaneously hypertensive rats to 1,25(OH)2D3in vivo. Calcium absorption in spontaneously hypertensive rats (SHR) has been reported to be increased, decreased or not different from their normo-tensive 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 1,25D3only 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 duodenal45Ca 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 × 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 1,25D3treated 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 × 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 duodenal45Ca uptake, measured in the conscious awake state, was higher in 35-week-old SHR (70.9 vs. 53.0%). Fourth, prior parathyroidectomy did not abolish the accentuated response in duodenal45Ca uptake by 1,25D3treated SHR (85.4 vs. 69.4%). These data indicate in vivo hypersensitivity to 1,25D3in the SHR, independent of hypertension and consistent with the postulate of intrinsic epithelial transport abnormalities.