Touyz R M, Schiffrin E L
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Am J Hypertens. 1995 Dec;8(12 Pt 1):1214-21. doi: 10.1016/0895-7061(95)00249-9.
Insulin influences platelet function by reducing platelet responsiveness to vasoactive agonists. In hypertension these insulin-related inhibitory effects are blunted. The aim of this study was to determine whether platelet sensitivity to insulin is affected after 12 weeks of antihypertensive treatment with calcium channel blockers. Eleven patients with essential hypertension and non-insulin-dependent diabetes were treated with either isradipine or diltiazem. Platelet free calcium concentration was measured spectrofluorometrically in nonstimulated and in angiotensin II (1 nmol/L)-stimulated platelets that had been pre-exposed to insulin (70 microU/mL). Platelets were studied before therapy and after 12 weeks of treatment. Systolic blood pressure and mean arterial pressure decreased significantly during treatment. Both calcium channel blockers equally decreased fasting serum insulin levels (from 138 +/- 2.7 pmol/L before therapy to 106 +/- 9.9 pmol/L after therapy). Results with both calcium channel antagonists were similar and have been pooled. In the pretreatment phase, insulin pre-incubation had no effect on angiotensin II-stimulated intracellular free calcium and responses to angiotensin II were similar in the absence (265 +/- 10.5 nmol/L) and presence of insulin (233 +/- 12.1 nmol/L). After treatment with calcium channel blockers, insulin significantly (P < .001) reduced angiotensin II-induced rise of intracellular free calcium from 214 +/- 7.7 nmol/L (absence of insulin) to 153 +/- 9.3 nmol/L (presence of insulin). Whether these effects are due specifically to calcium channel blockers or whether they are the result of lowering of blood pressure remains unclear. Serum insulin levels were positively correlated with angiotensin II-stimulated increase in intracellular free calcium in platelets pre-exposed to insulin, (r = 0.46; P < .05) suggesting that with increasing levels of insulin resistance, the inhibitory effects of insulin are reduced. This study shows that treatment of non-insulin-dependent diabetic hypertensive patients with these calcium channel blockers reduces hyperinsulinemia and increases sensitivity of platelets to the inhibitory effect of insulin on angiotensin II-stimulated calcium responses.
胰岛素通过降低血小板对血管活性激动剂的反应性来影响血小板功能。在高血压患者中，这些与胰岛素相关的抑制作用会减弱。本研究的目的是确定使用钙通道阻滞剂进行12周抗高血压治疗后，血小板对胰岛素的敏感性是否受到影响。11例原发性高血压合并非胰岛素依赖型糖尿病患者接受了伊拉地平或地尔硫䓬治疗。采用荧光分光光度法测定预先暴露于胰岛素（70微单位/毫升）的未刺激血小板以及血管紧张素II（1纳摩尔/升）刺激的血小板中的游离钙浓度。在治疗前和治疗12周后对血小板进行研究。治疗期间收缩压和平均动脉压显著下降。两种钙通道阻滞剂均同样降低空腹血清胰岛素水平（从治疗前的138±2.7皮摩尔/升降至治疗后的106±9.9皮摩尔/升）。两种钙通道拮抗剂的结果相似，已合并分析。在治疗前阶段，胰岛素预孵育对血管紧张素II刺激的细胞内游离钙无影响，在无胰岛素（265±10.5纳摩尔/升）和有胰岛素（233±12.1纳摩尔/升）的情况下，对血管紧张素II的反应相似。使用钙通道阻滞剂治疗后，胰岛素显著（P<.001）降低了血管紧张素II诱导的细胞内游离钙升高，从无胰岛素时的214±7.7纳摩尔/升降至有胰岛素时的153±9.3纳摩尔/升。这些作用是具体归因于钙通道阻滞剂，还是血压降低的结果尚不清楚。血清胰岛素水平与预先暴露于胰岛素的血小板中血管紧张素II刺激的细胞内游离钙增加呈正相关（r=0.46；P<.05），表明随着胰岛素抵抗水平的升高，胰岛素的抑制作用减弱。本研究表明，用这些钙通道阻滞剂治疗非胰岛素依赖型糖尿病高血压患者可降低高胰岛素血症，并增加血小板对胰岛素对血管紧张素II刺激的钙反应的抑制作用的敏感性。
