Adventitial NADPH oxidase‐4 in vascular oxidative stress (693.12)

BACKGROUND: Many types of hypertension are associated with increased level of angiotensin II and vascular oxidative stress. Previously, we have shown that NOX2, an adventitial NADPH oxidase (NOX) isoform, generates reactive oxygen species in cardiac vascular system. Although NOX4, as another major isoform of NOX, has been reported to generate reactive oxygen species and play a detrimental role, current publications allude to the possibility that NOX4 may play a beneficial role in the blood vessels. The current project examined this aspect by investigating the expression of adventitial NOX4 and reactive oxygen species. OBJECTIVE: The objective of this study is to test our hypothesis that the expression of adventitial NOX4 would not increase vascular ROS in Angiotensin II‐induced hypertension. METHOD: Four C57BL and NOX2 knockout mice, sixteen to eighteen weeks of age, were separated into two groups, a normotensive and Angiotensin II infused group. Angiotensin II infused animals developed hypertension. Thoracic aortas were sterilely removed, embedded in paraffin and then fixed on glass slides as 5µm thick sections. Expression of 3’‐nitrotyrosine, a reactive oxygen species indicator, NOX2, and NOX4 were determined by immunoflorescence method. RESULTS AND CONCLUSION: Similar to NOX2, NOX4 is expressed in both endothelium and adventitia of the aorta. The level of NOX4 in the Angiotensin II‐infused hypertensive is greatly increased about seven times in comparison to normotensive group. 3’‐Nitrotyrosin levels are increased in Angiotensin II infused mouse aorta segments. However, Angiotensin II induced hypertension and NT is not increased in NOX2 knockout mouse while there is significant amount of NOX4 is still expressed. In conclusion, our data indicate that NOX2 but not NOX4 contributes to vascular production of reactive oxygen species and hypertension. Grant Funding Source : Brock University