Haffner Dieter, Hocher Berthold, Müller Dominik, Simon Katja, König Kai, Richter Claus-Michael, Eggert Barbara, Schwarz Johanna, Godes Michael, Nissel Richard, Querfeld Uwe
Center for Cardiovascular Research, Charité Hospital, Humboldt University at Berlin, Germany.
J Hypertens. 2005 May;23(5):1067-75. doi: 10.1097/01.hjh.0000166849.72721.1c.
Vitamin D may contribute to cardiovascular disease in the absence of hypercalcemia in patients with chronic kidney disease.
We investigated the effects of long-term (6-week) treatment with 1,25(OH)2D3, at a non-hypercalcemic dosage (0.25 microg/kg per day per orally) in 5/6 nephrectomized rats: (i) vehicle-treated, sham-operated rats; (ii) 1,25(OH)2D3-treated, sham-operated rats; (iii) vehicle-treated, 5/6 nephrectomized rats; and (iv) 1,25(OH)2D3-treated, 5/6 nephrectomized rats.
Creatinine clearance after 6 weeks was significantly lower and parathyroid hormone levels were significantly higher in 1,25(OH)2D3-treated uremic rats, compared with uremic controls (P < 0.01). Serum calcium levels, as well as the calcium-phosphorus product, did not differ between both groups. Mean systolic blood pressure in 1,25(OH)2D3-treated animals was significantly increased, compared with vehicle (each P < 0.01). In addition, 1,25(OH)2D3-treated uremic animals showed left ventricular hypertrophy. Diffuse aortic calcification involving the intima and media layer occurred in 1,25(OH)2D3-treated uremic animals, but not in other groups. The mean aortic wall area and lumen area were increased two-fold in 1,25(OH)2D3-treated uremic animals compared with vehicle (P < 0.01), whereas the wall/lumen ratio remained unchanged, indicating fusiform aneurysm formation.
Hypertension, left ventricular hypertrophy, aortic calcification, and aneurysm, without hypercalcemia, occurred in 1,25(OH)2D3-treated, 5/6 nephrectomized rats. These data indicate a permissive effect of uremia for cardiovascular damage induced by non-hypercalcemic doses of 1,25(OH)2D3.
在慢性肾病患者中，维生素D可能在无高钙血症的情况下导致心血管疾病。
我们研究了以非高钙血症剂量（每天每千克口服0.25微克）的1,25(OH)₂D₃对5/6肾切除大鼠进行长期（6周）治疗的效果：（i）给予赋形剂治疗的假手术大鼠；（ii）给予1,25(OH)₂D₃治疗的假手术大鼠；（iii）给予赋形剂治疗的5/6肾切除大鼠；以及（iv）给予1,25(OH)₂D₃治疗的5/6肾切除大鼠。
与尿毒症对照组相比，接受1,25(OH)₂D₃治疗的尿毒症大鼠6周后的肌酐清除率显著降低，甲状旁腺激素水平显著升高（P < 0.01）。两组之间的血清钙水平以及钙磷乘积没有差异。与赋形剂组相比，接受1,25(OH)₂D₃治疗的动物的平均收缩压显著升高（各P < 0.01）。此外，接受1,25(OH)₂D₃治疗的尿毒症动物出现左心室肥厚。接受1,25(OH)₂D₃治疗的尿毒症动物发生了累及内膜和中膜层的弥漫性主动脉钙化，但其他组未出现。与赋形剂组相比，接受1,25(OH)₂D₃治疗的尿毒症动物的平均主动脉壁面积和管腔面积增加了两倍（P < 0.01），而壁/腔比值保持不变，表明形成了梭形动脉瘤。
在接受1,25(OH)₂D₃治疗的5/6肾切除大鼠中，出现了高血压、左心室肥厚、主动脉钙化和动脉瘤，且无高钙血症。这些数据表明尿毒症对非高钙血症剂量的1,25(OH)₂D₃诱导的心血管损伤具有促进作用。
