Koh Kwang Kon, Ahn Jeong Yeal, Han Seung Hwan, Kim Dae Sung, Jin Dong Kyu, Kim Hyung Sik, Shin Mi-Seung, Ahn Tae Hoon, Choi In Suck, Shin Eak Kyun
Department of Cardiology, Vascular Medicine and Atherosclerosis Unit, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea 405-760.
J Am Coll Cardiol. 2003 Sep 3;42(5):905-10. doi: 10.1016/s0735-1097(03)00846-5.
We investigated the vascular effects of candesartan in hypertensive patients.
The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed.
We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design.
Candesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 +/- 0.07 to 1.29 +/- 0.09 microM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 +/- 0.24 to 6.22 +/- 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 +/- 8 to 190 +/- 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 +/- 4 to 53 +/- 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (-0.247 < or = r < or = 0.195) and between these changes and reduction of diastolic BP (-0.262 < or = r < or = 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (-0.119 < or = r < or = 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = -0.162).
Inhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.
我们研究了坎地沙坦对高血压患者血管的影响。
肾素 - 血管紧张素系统可能通过促进内皮功能障碍而导致动脉粥样硬化形成。可能的机制是血管紧张素II促进超氧阴离子生成、内皮功能障碍、炎症和纤维蛋白溶解受损。坎地沙坦对这些情况的影响尚未明确观察到。
我们对45例轻度至中度高血压患者在两个月内每日给予安慰剂或16毫克坎地沙坦。这是一项随机、双盲、安慰剂对照的交叉研究。
坎地沙坦未显著改变脂蛋白水平。然而，与安慰剂相比，坎地沙坦显著降低血浆丙二醛水平，从1.50±0.07微摩尔降至1.29±0.09微摩尔（p = 0.009）；将血流介导的充血扩张反应百分比从5.17±0.24%提高到6.22±0.26%（p < 0.001）；此外，降低血浆单核细胞趋化蛋白（MCP - 1）水平，从213±8皮克/毫升降至190±7皮克/毫升（p = 0.003），肿瘤坏死因子 - α从2.93皮克/毫升降至2.22皮克/毫升（p = 0.026）以及纤溶酶原激活物抑制剂1型从74±4纳克/毫升降至53±4纳克/毫升（p < 0.001），但对C反应蛋白（CRP）、基质金属蛋白酶蛋白和纤维蛋白原无影响。这些变化与收缩压降低（-0.247≤r≤0.195）以及与舒张压降低（-0.262≤r≤0.197）之间均无显著相关性。炎症标志物与血流介导的扩张百分比或氧化应激降低之间也无显著相关性（-0.119≤r≤0.127）。此外，我们观察到CRP与MCP - 1水平之间无显著相关性（r = -0.162）。
在高血压患者中抑制血管紧张素II 1型（AT1）受体可逆转内皮功能障碍，表现为血流介导的扩张和纤维蛋白溶解改善以及氧化应激和炎性细胞因子降低，提示AT1受体阻滞剂治疗具有抗动脉粥样硬化作用。
