Abstract DP351: Angiotensin-II Induced Hypertension Upregulates The Brain Endothelial CD38 Contributing To Cerebrovascular Oxidative Injury

Introduction: CD38 is a multifunctional enzyme that plays a central role in NAD+ metabolism. Emerging evidence implicates it in oxidative stress injury and endothelial cells (ECs) dysfunction. We hypothesized that angiotensin-II (Ang-II) induced hypertension (HTN) upregulates CD38 in the brain ECs contributing to cerebrovascular oxidative injury. Methods: The early changes of CD38 expression and activity in response to Ang-II were resolved in vitro in a model of human brain primary microvascular endothelial cells (HBPMECs). CD38 loss of function effect was assessed by CD38 silencing siRNA. We measured CD38 expression by immunofluorescence (IF) and western blotting, enzymatic activity, superoxide (DHE- Dihydroethidium) generation, NAD(P)H level, and nitric oxide (NO) (DAF-diaminofluorescein) level. CD38 expression in vivo was examined in (10-13) week-old male C57BL/6J mice using Ang-II (non-pressor dose: 100 ng/kg/min or slow pressor dose: 600 ng/kg/min) and control saline delivered by subcutaneous miniosmotic pumps (N=16). Results: HBPMECs treatment with Ang-II rapidly increased CD38 enzymatic function within 5 min by 38% (p=0.035) which was accompanied by 31% NAD(P)H decrease (p=0.001). A 2.4-fold increase in CD38 expression was found after 120 min of Ang-II exposure (p