Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Korean Med Sci. 2010 Sep;25(9):1305-12. doi: 10.3346/jkms.2010.25.9.1305. Epub 2010 Aug 14.
Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
噻嗪类药物已知可减少尿钙排泄。我们假设噻嗪类药物对引起高钙尿症的刺激具有不同的降低尿钙作用。在高钙饮食和维生素 D3 诱导的高钙尿症大鼠中，评估了氢氯噻嗪（HCTZ）的降钙作用以及瞬时受体电位香草醛 5（TRPV5）、钙结合蛋白-D28K（calbindin-D28K）和几种钠转运体的表达。从 4 组 Sprague-Dawley 大鼠中测量尿钙排泄和转运体的表达；对照组、HCTZ 组、高钙-维生素 D 组和高钙-维生素 D 加 HCTZ 组。在 HCTZ 组中，HCTZ 使尿钙排泄减少了 51.4%，而在高钙-维生素 D 加 HCTZ 组中仅减少了 15%。与高钙-维生素 D 组相比，HCTZ 并未改变高钙-维生素 D 加 HCTZ 组中 TRPV5 蛋白的丰度。在高钙尿症大鼠中，NHE3、SGLT1 和 NKCC2 的蛋白丰度降低，而仅在高钙尿症大鼠中 SGLT1 蛋白丰度增加。HCTZ 的降钙作用在高钙和维生素 D 诱导的高钙尿症大鼠中减弱。这种减弱似乎是由于在高钙和维生素 D 诱导的严重高钙尿症情况下，HCTZ 对 TRPV5 蛋白丰度缺乏作用所致。
