Department of Internal Medicine and Therapeutics, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy.
Hypertens Res. 2011 Apr;34(4):509-15. doi: 10.1038/hr.2010.260. Epub 2010 Dec 23.
The aim of this study was to evaluate the effects of imidapril and candesartan on fibrinolysis and insulin sensitivity in normoweight hypertensive patients. After a 2-week wash-out period, 61 patients with mild-to-moderate hypertension were randomized to imidapril or candesartan for 12 weeks. Blood pressure (BP), plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen activities were evaluated at baseline and during treatment. The patients underwent a euglycemic-hyperinsulinemic clamp (insulin sensitivity was evaluated as glucose infusion rate during the last 30 min) and a desmopressin test (with desmopressin infusion in the brachial artery) to evaluate endothelial ability to release t-PA. Imidapril and candesartan induced similar systolic/diastolic BP reductions (-16/12.6 and -16.1/12.2 mm Hg, respectively, P<0.001 vs. baseline). Imidapril increased glucose infusion rate (+1.1 mg min(-1) per kg, P<0.02), whereas candesartan did not change it. Both drugs decreased PAI-1 antigen activity after 4 weeks of treatment; subsequently, only the decreasing effect of imidapril was sustained throughout the 12 weeks, whereas candesartan increased PAI-1 activity at week 12 (P<0.05 vs. baseline, P<0.01 vs. imidapril). Activity of t-PA decreased with candesartan (from 0.48±0.16 to 0.43±0.14 IU ml(-1), P<0.05) but not with imidapril. Activity of t-PA in response to desmopressin was increased more by imidapril (+4.45 IU ml(-1)) than by candesartan (+2.73 IU ml(-1), P<0.01 vs. imidapril). These results indicate that in normoweight hypertensive patients, despite similar BP reduction, imidapril but not candesartan improved the fibrinolytic balance, suggesting that mechanisms other than Ang II inhibition, possibly including bradykinin-mediated effects on insulin sensitivity and endothelial function, may be responsible for these different effects.
这项研究的目的是评估依那普利和坎地沙坦对正常体重高血压患者纤溶和胰岛素敏感性的影响。在为期 2 周的洗脱期后，61 例轻中度高血压患者被随机分为依那普利或坎地沙坦组，治疗 12 周。在基线和治疗期间评估血压（BP）、血浆组织型纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制剂-1（PAI-1）抗原活性。患者接受了正葡萄糖高胰岛素钳夹（评估最后 30 分钟的葡萄糖输注率作为胰岛素敏感性）和去氨加压素试验（在肱动脉中输注去氨加压素），以评估内皮释放 t-PA 的能力。依那普利和坎地沙坦引起相似的收缩压/舒张压降低（分别为-16/12.6 和-16.1/12.2mmHg，P<0.001 与基线相比）。依那普利增加了葡萄糖输注率（+1.1mg min(-1) per kg，P<0.02），而坎地沙坦没有改变。两种药物在治疗 4 周后均降低了 PAI-1 抗原活性；随后，只有依那普利的降低作用持续了 12 周，而坎地沙坦在第 12 周增加了 PAI-1 活性（P<0.05 与基线相比，P<0.01 与依那普利相比）。t-PA 活性随坎地沙坦降低（从 0.48±0.16 降至 0.43±0.14IU ml(-1)，P<0.05），但不受依那普利影响。依那普利引起的 t-PA 对去氨加压素的反应增加（+4.45IU ml(-1)）多于坎地沙坦（+2.73IU ml(-1)，P<0.01 与依那普利相比）。这些结果表明，在正常体重的高血压患者中，尽管降压作用相似，但依那普利而非坎地沙坦改善了纤溶平衡，提示除了 Ang II 抑制之外，可能包括缓激肽介导的对胰岛素敏感性和内皮功能的影响，可能是这些不同作用的原因。
