ACEI抗动脉粥样硬化作用 从基础理论到临床实践PPT.pptVIP

心脏预后预防评估(HOPE)亚研究比较了ACEI 两种剂量下(10 mg and 2.5 mg/天)对446名可评价患者的LV重量和功能的效应。结果显示了一个显著的剂量依赖性效应。1 4年后，在安慰剂组和ACEI 2.5-mg组 LV的重量都增加。相反，在ACEI 10-mg组LV的重量下降了3.53 g(P = 0.03)。 在安慰剂组和ACEI 2.5 mg 组中LV收缩期终末容积增加，而ACEI 10 mg 组LV收缩期终末容积却减少了1.90 mL (P = 0.001) 。 1. Lonn E, Shaikholeslami R, Yi Q, Bosch J, Sullivan B, Tanser P, et al. Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: A substudy of the Heart Outcomes Prevention Evaluation (HOPE) Trial. J Am Coll Cardiol. 2004;43:2200-2206. To ensure elevated baseline levels of PAI-1, Brown et al treated 20 insulin-resistant hypertensive patients with hydrochlorothiazide 12.5 mg. Subjects were then randomized to ACEI (n = 9) or losartan (n = 11) for 6 weeks.1 Dosing was adjusted to achieve a diastolic BP 90 mm Hg. At 1 week, both treatments significantly decreased PAI-1 antigen levels (P = 0.046). At 3 weeks, however, PAI-1 levels had returned to baseline in the losartan group. PAI-1 antigen levels in the ACEI group remained significantly decreased from baseline at 3 and 6 weeks. 1. Brown NJ, Kumar S, Painter CA, Vaughan DE. ACE inhibition versus angiotensin type 1 receptor antagonism: Differential effects on PAI-1 over time. Hypertension. 2002;40:859-865. Ang II induces PAI-1 release. In contrast, bradykinin induces tissue plasminogen activator (tPA) release. Matsumoto et al randomized 45 hypertensive patients with atypical chest pain to a 4-week treatment with ACEI 4 mg, losartan 50 mg, or no treatment (control).1 Immediately after the final dose, graded doses of bradykinin were administered into the left coronary artery. In a dose-dependent manner, bradykinin increased coronary blood flow, coronary vasomotor responses, and tPA in all 3 groups. ACEI and losartan augmented bradykinin-mediated vasodilation to similar extents (data not shown). However, as shown, tPA levels in the ACEI group were significantly