Department of Pharmacology, Université de Montréal, Quebec, Canada.
Am J Hypertens. 2011 Nov;24(11):1239-44. doi: 10.1038/ajh.2011.137. Epub 2011 Aug 11.
Inflammation and oxidative stress have been identified as integral parts in the pathogenesis of hypertension. Cyclo-oxygenase-2 which could elicit inflammation and free radicals generation appears to be a key enzyme in hypertension. Cyclo-oxygenase-2 expression and oxidative stress in cardiovascular tissues are increased in the angiotensin II model.
Cyclo-oxygenase-1 and cyclo-oxygenase-2 deficient mice and their cultured aortic smooth muscle cells were used to investigate the role of these enzymes in angiotensin II induced superoxide production and hypertension.
At resting state, the superoxide production in aortic and cardiac tissues was lower in cyclo-oxygenase-2 deficient than in the wild type or in cyclo-oxygenase-1 deficient mice. Chronic angiotensin II infusion increased the superoxide production in these tissues from both cyclo-oxygenase-deficient and wild-type mice whereas the level in cyclo-oxygenase-2 deficient mice was equivalent to the basal level in wild-type mice. The hypertensive effect of angiotensin II was attenuated in cyclo-oxygenase-2 deficient mice. Aspirin treatment reduced the basal superoxide production and blunted the oxidative and hypertensive effect of angiotensin II in wild type and cyclo-oxygenase-1 deficient mice whereas it lost completely its antioxidative property in angiotensin II-treated aortic smooth muscle cells isolated from cyclo-oxygenase-2 deficient mice.
Cyclo-oxygenase-2 pathway plays a major role in the superoxide generation as well as in the angiotensin II-induced oxidative stress and blood pressure. Cyclo-oxygenase-1 activity didn't show any influence on these parameters. These results suggest that cyclo-oxygenase-2 is involved in the pathogenesis of hypertension.
炎症和氧化应激被认为是高血压发病机制的组成部分。环氧化酶-2 可以引发炎症和自由基的产生，似乎是高血压的关键酶。血管紧张素 II 模型中，心血管组织中环氧化酶-2 的表达和氧化应激增加。
使用环氧化酶-1 和环氧化酶-2 缺乏小鼠及其培养的主动脉平滑肌细胞，研究这些酶在血管紧张素 II 诱导的超氧产生和高血压中的作用。
在静息状态下，环氧化酶-2 缺乏小鼠的主动脉和心脏组织中超氧产生低于野生型或环氧化酶-1 缺乏小鼠。慢性血管紧张素 II 输注增加了这些组织中环氧化酶缺乏和野生型小鼠的超氧产生，而环氧化酶-2 缺乏小鼠的水平相当于野生型小鼠的基础水平。血管紧张素 II 的高血压作用在环氧化酶-2 缺乏小鼠中减弱。阿司匹林治疗降低了基础超氧产生，并减弱了野生型和环氧化酶-1 缺乏小鼠中血管紧张素 II 的氧化和高血压作用，而在环氧化酶-2 缺乏小鼠的血管紧张素 II 处理的主动脉平滑肌细胞中，它完全失去了抗氧化作用。
环氧化酶-2 途径在超氧产生以及血管紧张素 II 诱导的氧化应激和血压中起主要作用。环氧化酶-1 活性对这些参数没有影响。这些结果表明，环氧化酶-2 参与了高血压的发病机制。
