Division of Clinical Pharmacology, 536 Robinson Research Building, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Hypertension. 2011 Aug;58(2):232-9. doi: 10.1161/HYPERTENSIONAHA.111.172718. Epub 2011 Jul 5.
Previous studies indicate that superoxide is important in the modulation of blood pressure but have not specifically identified the cell types or organs involved. We created mice with loxP sites flanking the extracellular superoxide dismutase (SOD3) gene. These mice were crossed with mice expressing inducible Cre-recombinase driven by the smooth muscle myosin heavy chain promoter allowing tissue-specific deletion of SOD3. Deletion of SOD3 increased vascular superoxide and reduced vascular NO levels as detected by electron spin resonance. Despite these changes in NO and superoxide, we did not observe increases in vascular inflammation caused by angiotensin II. Moreover, deletion of vascular SOD3 did not augment hypertension in response to angiotensin II. In additional studies, we also deleted SOD3 from the circumventricular organs by intracerebroventricular injection of an adenovirus encoding Cre-recombinase. Although this raised blood pressure and augmented the hypertension caused by angiotensin II, these responses were not further increased by vascular deletion of SOD3. These data suggest that the extracellular superoxide dismutase in vascular smooth muscle is not involved in the genesis of angiotensin II-induced hypertension and further emphasize the role of central SOD3 in the modulation of blood pressure.
先前的研究表明超氧化物在血压调节中很重要，但并未具体确定涉及的细胞类型或器官。我们创建了带有loxP 位点侧翼的细胞外超氧化物歧化酶（SOD3）基因的小鼠。这些小鼠与表达由平滑肌肌球蛋白重链启动子驱动的诱导型 Cre 重组酶的小鼠交配，允许 SOD3 的组织特异性缺失。SOD3 的缺失增加了血管中的超氧化物并降低了血管中的 NO 水平，这是通过电子自旋共振检测到的。尽管 NO 和超氧化物发生了这些变化，但我们没有观察到血管炎症因血管紧张素 II 而增加。此外，血管 SOD3 的缺失也不会增强血管紧张素 II 引起的高血压。在其他研究中，我们还通过脑室内注射编码 Cre 重组酶的腺病毒从脑周围器官中删除 SOD3。尽管这会升高血压并增强血管紧张素 II 引起的高血压，但血管 SOD3 的缺失并没有进一步增加这些反应。这些数据表明血管平滑肌中的细胞外超氧化物歧化酶不参与血管紧张素 II 诱导的高血压的发生，并进一步强调了中枢 SOD3 在血压调节中的作用。
