Roullet C M, Roullet J B, Martin A S, McCarron D A
Division of Nephrology, Hypertension, and Clinical Pharmacology, Oregon Health Sciences University, Portland 97201.
Hypertension. 1994 Aug;24(2):176-82. doi: 10.1161/01.hyp.24.2.176.
The abnormal intestinal Ca2+ transport reported in spontaneously hypertensive rats (SHR) has been attributed to decreased responsiveness to calcitriol. We reexamined this hypothesis by studying the calcitriol regulation of SHR duodenal calbindin-D9K and calmodulin and the relation of calcitriol to Ca2+ uptake by isolated enterocytes. SHR and normotensive Wistar-Kyoto (WKY) rats were injected with either 50 ng/d calcitriol (vit-D) or vehicle alone (control) for 3 days. Decreased calbindin-D9K (P < .001) and cellular Ca2+ flux (P < .001) were observed in control SHR. Calcitriol increased total cell and brush border calbindin-D9K (P < .0001); this variation paralleled plasma calcitriol levels in both strains. In contrast, Ca2+ flux, which increased in vit-D animals, remained lower in SHR for plasma calcitriol levels similar to those in WKY rats. Immunoreactive calmodulin was similar in both strains whether assayed in total cell or brush border membranes. In contrast, when measured by ligand blotting (45Ca), calmodulin was lower in SHR than in WKY rats (P < .01), suggesting the existence of a calmodulin pool with reduced Ca2+ binding capacity in the hypertensive strain. Calcitriol had no effect on calmodulin in either strain. In conclusion, Ca2+ binding protein regulation by calcitriol is normal in the SHR, and decreased hormone responsiveness cannot account for the defective duodenal calcium transport of this experimental model of hypertension.
自发性高血压大鼠（SHR）中报道的肠道钙转运异常被归因于对骨化三醇的反应性降低。我们通过研究骨化三醇对SHR十二指肠钙结合蛋白-D9K和钙调蛋白的调节以及骨化三醇与分离的肠细胞对钙摄取的关系，重新审视了这一假设。给SHR和血压正常的Wistar-Kyoto（WKY）大鼠分别注射50 ng/d的骨化三醇（维生素D）或单独注射载体（对照），持续3天。在对照SHR中观察到钙结合蛋白-D9K减少（P <.001）和细胞钙通量降低（P <.001）。骨化三醇增加了总细胞和刷状缘钙结合蛋白-D9K（P <.0001）；这种变化与两种品系的血浆骨化三醇水平平行。相比之下，在维生素D处理的动物中增加的钙通量，在SHR中对于与WKY大鼠相似的血浆骨化三醇水平仍然较低。无论是在总细胞膜还是刷状缘膜中检测，免疫反应性钙调蛋白在两种品系中相似。相比之下，当通过配体印迹法（45Ca）测量时，SHR中的钙调蛋白低于WKY大鼠（P <.01），表明在高血压品系中存在钙结合能力降低的钙调蛋白池。骨化三醇对两种品系的钙调蛋白均无影响。总之，在SHR中骨化三醇对钙结合蛋白的调节是正常的，激素反应性降低不能解释这种高血压实验模型十二指肠钙转运缺陷。
