Smooth Muscle Research Program, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada.
Eur J Pharmacol. 2010 May 25;634(1-3):107-12. doi: 10.1016/j.ejphar.2010.02.006. Epub 2010 Feb 13.
In rat mesenteric arteries we have recently found that perivascular adipose tissue (PVAT) promoted vasoconstriction to perivascular neuronal activation (by electrical field stimulation, EFS) through generation of superoxide. In this study, we examined the role of adipocyte-generated angiotensin II in PVAT-mediated potentiation of contraction to nerve stimulation. In rat mesenteric PVAT, the presence of angiotesinogen and angiotensin I-converting enzyme (ACE) mRNA was confirmed by RT-PCR. Immunohistochemical staining showed the presence of angiotensin II in mesenteric PVAT. In rat mesenteric arteries, treatment of the vessels with an ACE inhibitor (enalaprilat) or angiotensin II type 1 receptor antagonist (candesartan) reduced PVAT-mediated potentiation of EFS-induced contraction. Exogenously applied angiotensin II enhanced EFS-induced contraction in arteries without PVAT, but not in the arteries with intact PVAT. Chronic treatment with an ACE inhibitor quinapril (14 days) lowered blood pressure and alleviated the potentiation effects of PVAT in EFS-induced contraction. Mesenteric arteries from quinapril-treated group now exhibited the potentiation response to exogenously applied angiotensin II in arteries with intact PVAT to a comparable level as in arteries with PVAT removed. Treatment with hydralazine reduced blood pressure to the same level as quinapril treatment, but did not affect PVAT-associated potentiation of vasoconstriction to EFS and the response to exogenously applied angiotensin II in PVAT-intact arteries. These results showed that adipocyte-derived angiotensin II is critically involved in PVAT-mediated potentiation of EFS-evoked contraction in rat mesenteric arteries.
在大鼠肠系膜动脉中，我们最近发现，血管周围脂肪组织（PVAT）通过产生超氧化物促进血管收缩对血管周围神经元的激活（通过电刺激，EFS）。在这项研究中，我们研究了脂肪细胞生成的血管紧张素 II 在 PVAT 介导的神经刺激收缩增强中的作用。在大鼠肠系膜 PVAT 中，通过 RT-PCR 证实了血管紧张素原和血管紧张素 I 转换酶（ACE）mRNA 的存在。免疫组织化学染色显示血管紧张素 II 存在于肠系膜 PVAT 中。在大鼠肠系膜动脉中，用 ACE 抑制剂（依那普利）或血管紧张素 II 型 1 受体拮抗剂（坎地沙坦）处理血管可降低 PVAT 介导的 EFS 诱导收缩增强。外源性应用血管紧张素 II 增强了无 PVAT 的动脉中 EFS 诱导的收缩，但在完整 PVAT 的动脉中则没有。用 ACE 抑制剂喹那普利（14 天）慢性处理降低了血压并减轻了 PVAT 在 EFS 诱导的收缩中的增强作用。来自喹那普利处理组的肠系膜动脉现在在具有完整 PVAT 的动脉中显示出对血管紧张素 II 的增强反应，与去除 PVAT 的动脉中相似。肼屈嗪处理将血压降低到与喹那普利处理相同的水平，但不影响 EFS 引起的血管收缩增强和血管紧张素 II 对完整 PVAT 动脉的反应。这些结果表明，脂肪细胞衍生的血管紧张素 II 是血管周围脂肪组织介导的大鼠肠系膜动脉 EFS 诱发收缩增强的关键因素。
