Glitazones and heart failure - Critical appraisal for the clinician
Glitazones and heart failure - Critical appraisal for the clinician
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DOI：
10.1161/01.cir.0000054675.30348.9a
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发表时间：
2003-03-18
期刊：
影响因子：
37.8
通讯作者：
Verma, S
中科院分区：
文献类型：
--
作者：
Wang, CH;Weisel, RD;Verma, S
越来越多的证据表明，胰岛素刺激内皮依赖性一氧化氮介导的血管舒张，并且这种作用与胰岛素对葡萄糖处置的总体作用密切相关。13，14重要的是，胰岛素介导的血管舒张在胰岛素抵抗（也称为血管胰岛素抵抗）患者中是钝化的。13，15除了NO介导的血管舒张功能降低外，胰岛素抵抗患者通常同时存在高胰岛素血症，这是内皮素产生增加的刺激因素，从而进一步损害内皮功能并增加血管张力。13格列酮改善胰岛素敏感性可对抗血管胰岛素抵抗，减少高胰岛素血症诱导的内皮素-1产生，从而改善紧张性血管扩张剂对胰岛素的反应，降低外周血管阻力和血压。通过降低血浆胰岛素水平，这些药物可降低胰岛素的血压升高作用，如肾钠潴留和交感神经活动增加。16格列酮的上述血管效应可能通过降低后负荷和外周血管阻力为心力衰竭患者提供优势。事实上，在曲格列酮治疗的患者中，外周阻力降低导致每搏输出量和心输出量增加。17早期的曲格列酮研究显示舒张压显著降低6.5 mm Hg（8%）。17同样，罗格列酮（4 mg，每日两次，持续52周）与收缩压（3.5 mmHg）和舒张压（2.7 mmHg）显著降低相关。虽然后负荷和血压的降低理论上对糖尿病心力衰竭患者有益，但仍需仔细评估。
There is accumulating evidence to suggest that insulin stimulates endothelium-dependent nitric oxide-mediated vasodilatation, and that this effect is closely associated with the overall effects of insulin on glucose disposal. 13, 14 Importantly, insulin-mediated vasorelaxation is blunted in patients with insulin resistance (also known as vascular insulin resistance). 13, 15 In addition to decreased NO-mediated vasorelaxation, patients with insulin resistance often have coexistent hyperinsulinemia, which is a stimulus for enhanced endothelin production, thereby further impairing endothelial function and increasing vascular tone. 13 Improving insulin sensitivity with glitazones may counter vascular insulin resistance and reduce hyperinsulinemia-induced endothelin-1 production, resulting in improved tonic vasodilator response to insulin and reduction in peripheral vascular resistance and blood pressure. By reducing plasma insulin levels, these agents may reduce the blood-pressure-raising actions of insulin such as renal sodium retention and increased sympathetic activity. 16The aforementioned vascular effects of glitazones may offer an advantage to patients with heart failure by decreasing afterload and peripheral vascular resistance. Indeed, in troglitazonetreated patients, decreased peripheral resistance produced an increase in stroke volume and cardiac output. 17 Earlier studies with troglitazone demonstrated a significant reduction in diastolic blood pressure by 6.5 mm Hg (8%). 17 Likewise, rosiglitazone (4 mg twice a day over 52 weeks) is associated with a significant decrease in systolic blood pressure (3.5 mm Hg) and diastolic pressure (2.7 mmHg). Although reductions in afterload and blood pressure would theoretically be beneficial to diabetic patients with heart failure, this remains to be carefully evaluated.