Angiotensin II-induced modulation of endothelium-dependent relaxation in rabbit mesenteric resistance arteries
Angiotensin II-induced modulation of endothelium-dependent relaxation in rabbit mesenteric resistance arteries
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DOI：
10.1113/jphysiol.2002.034116
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发表时间：
2003-05-01
影响因子：
5.5
通讯作者：
Mabuchi, Y
中科院分区：
文献类型：
--
作者：
Itoh, T;Kajikuri, J;Mabuchi, Y
使用兔肠系膜阻力动脉研究局部内源性血管紧张素 II (Ang II) 在阻力动脉内皮功能中的作用。首先，在这些动脉中确认了免疫反应性 Ang II 以及 Ang II 1 型受体（AT、R）和血管紧张素转换酶（ACE）的存在。在完整的内皮试纸中，AT,R 阻滞剂奥美沙坦 (1 mum) 和 ACE 抑制剂 temocaprilat (1 mum) 各自增强去甲肾上腺素 (NA, 10 mum) 引起的收缩过程中乙酰胆碱 (0.03 mum) 诱导的松弛。使用 CV-11974（另一种 AT(1)R 阻滞剂）和 enalaprilat（另一种 ACE 抑制剂）也获得了类似的效果。一氧化氮合酶抑制剂N-G-硝基-L-精氨酸(L-NNA)消除了奥美沙坦的上述作用。在内皮剥脱的条带中，奥美沙坦增强了 NO 供体 NOC-7 (10 nm) 诱导的松弛。奥美沙坦对 cGMP 产生没有影响 (1) 在内皮完整的条带中（在不存在或存在 ACh 的情况下）或 (2) 在内皮剥脱的条带中（在不存在或存在 NOC-7 的情况下）。 β-七叶皂皮条带、8-溴鸟苷 3',5' 环单磷酸盐 (8-Br-cGMP, 0.01-1 mum) 浓度依赖性地抑制 (a) NA+GTP 存在下 0.3 mum Ca2+ 诱导的收缩和 (b) 0.2 mum Ca2++GTPyS 诱导的收缩。奥美沙坦显着增强 8-Br-cGMP 诱导的松弛，而 Ang II (0.1 nm) 显着抑制。我们提出了新的假设，即在这些动脉中，位于平滑肌细胞内的 Ang II 激活 AT(1)R，并至少部分通过抑制 cGMP 对这些细胞的作用来抑制 ACh 诱导的内皮依赖性松弛。
The role of local endogenous angiotensin II (Ang II) in endothelial function in resistance arteries was investigated using rabbit mesenteric resistance arteries. First, the presence of immunoreactive Ang II together with Ang II type-1 receptor (AT, R) and angiotensin converting enzyme (ACE) was confirmed in these arteries. In endothelium-intact strips, the AT,R-blocker olmesartan (I mum) and the ACE-inhibitor temocaprilat (1 mum) each enhanced the ACh (0.03 mum)-induced relaxation during the contraction induced by noradrenaline (NA, 10 mum). Similar effects were obtained using CV-11974 (another AT(1)R blocker) and enalaprilat (another ACE inhibitor). The nitric-oxidesynthase inhibitor N-G-nitro-L-arginine (L-NNA) abolished the above effect of olmesartan. In endothelium-denuded strips, olmesartan enhanced the relaxation induced by the NO donor NOC-7 (10 nm). Olmesartan had no effect on cGMP production (1) in endothelium-intact strips (in the absence or presence of ACh) or (2) in endothelium-denuded strips (in the absence or presence of NOC-7). beta-escin-skinned strips, 8-bromoguanosine 3',5' cyclic monophosphate (8-Br-cGMP, 0.01-1 mum) concentration dependently inhibited the contractions induced (a) by 0.3 mum Ca2+ in the presence of NA+GTP and (b) by 0.2 mum Ca2++GTPyS. Olmesartan significantly enhanced, while Ang II (0.1 nm) significantly inhibited, the 8-Br-cGMP-induced relaxation. We propose the novel hypothesis that in these arteries, Ang II localized within smooth muscle cells activates AT(1)Rs and inhibits ACh-induced, endothelium-dependent relaxation at least partly by inhibiting the action of cGMP on these cells.