Fliser D, Franek E, Fode P, Stefanski A, Schmitt C P, Lyons M, Ritz E
Department of Internal Medicine, Ruperto-Carola University, Heidelberg, Germany.
Nephrol Dial Transplant. 1997 May;12(5):933-8. doi: 10.1093/ndt/12.5.933.
Acute administration of parathyroid hormone (PTH) causes vasodilation and blood pressure decrease in experimental animals. This effect contrasts with the putative role of secondary hyperparathyroidism in the pathogenesis of hypertension of patients with renal failure. Uraemia is characterized by insulin resistance and hyperinsulinaemia. We therefore investigated whether subacute administration of physiological doses of human 1,34-PTH affects blood pressure under conditions of controlled insulin levels (euglycaemic clamp technique) in humans.
In a double-blind cross-over design 10 healthy male subjects received, on two occasions, in random order, for 2 h, either a sham infusion or an infusion of 200 units of 1,34-PTH.
Mean ionized calcium concentration increased significantly (P < 0.01) within the normal range during euglycaemic hyperinsulinaemia, both with sham infusion (from 1.25 +/- 0.04 to 1.29 +/- 0.02 mmol/l) and with infusion of 1,34-PTH, but the increase was more marked with 1,34-PTH administration (from 1.26 +/- 0.05 to 1.33 +/- 0.07). In addition, mean platelet intracellular calcium concentration (by fluorescence spectroscopy) was unchanged with sham infusion (49.9 +/- 4.1 versus 50.3 +/- 5.0 nmol), but increased significantly (P < 0.05; paired t-test) after 1,34-PTH infusion (from 49.8 +/- 5.0 to 52.8 +/- 5.8). The infusion of 1,34-PTH resulted in a significant (P < 0.01) increase in mean MAP (from 84 +/- 5 to 88 +/- 5 mmHg) as compared with sham infusion (85 +/- 4 versus 86 +/- 4). The intra-individual changes in intracellular calcium concentration (delta[Ca2+]i) were significantly correlated to the changes in mean MAP (delta MAP) (r = 0.87, P < 0.001). In contrast to blood pressure, insulin sensitivity was not affected by 1,34-PTH infusion (M-value: 7.2 +/- 1.6 mg/kg per min) as compared with sham infusion (7.3 +/- 1.4).
Subacute administration of physiological doses of parathyroid hormone under hyperinsulinaemic conditions significantly affects intracellular calcium and blood pressure in healthy subjects, but does not affect the action of insulin.
在实验动物中，急性给予甲状旁腺激素（PTH）可导致血管舒张和血压下降。这种效应与继发性甲状旁腺功能亢进在肾衰竭患者高血压发病机制中的假定作用形成对比。尿毒症的特征是胰岛素抵抗和高胰岛素血症。因此，我们研究了在人体胰岛素水平受控（正常血糖钳夹技术）的条件下，亚急性给予生理剂量的人1-34-PTH是否会影响血压。
在双盲交叉设计中，10名健康男性受试者分两次随机接受假输注或200单位1-34-PTH输注，每次持续2小时。
在正常血糖高胰岛素血症期间，无论是假输注（从1.25±0.04到1.29±0.02 mmol/L）还是输注1-34-PTH，平均离子钙浓度在正常范围内均显著升高（P<0.01），但1-34-PTH给药后的升高更为明显（从1.26±0.05到1.33±0.07）。此外，假输注时平均血小板细胞内钙浓度（通过荧光光谱法）无变化（49.9±4.1对50.3±5.0 nmol），但1-34-PTH输注后显著升高（P<0.05；配对t检验）（从49.8±5.0到52.8±5.8）。与假输注（85±4对86±4）相比，输注1-34-PTH导致平均MAP显著升高（P<0.01）（从84±5到88±5 mmHg）。细胞内钙浓度的个体内变化（δ[Ca2+]i）与平均MAP的变化（δMAP）显著相关（r = 0.87，P<0.001）。与血压不同，1-34-PTH输注对胰岛素敏感性无影响（M值：7.2±1.6 mg/kg每分钟），假输注时为（7.3±1.4）。
在高胰岛素血症条件下亚急性给予生理剂量的甲状旁腺激素会显著影响健康受试者的细胞内钙和血压，但不影响胰岛素的作用。
