Abstract 14020: Effect of Endothelial Specific Overexpression of a Destabilized Endothelial Nitric Oxide Synthase Variant on Blood Pressure and Vascular Endothelial Function

Essential hypertension is associated with endothelial dysfunction and reactive oxygen species (ROS) are considered to play a role here. To investigate whether dysfunctional vascular eNOS might contribute to the regulation of blood pressure we overexpressed two different eNOS variants by the endothelial specific tie-2 promoter. Hence wildtype eNOS (eNOS-tg) or respectively a destabilized eNOS (C101A-eNOS-tg) were introduced into the vasculature of C57BL/6 mice. Destabilization of eNOS was induced via replacement of a cysteine residue by alanine resulting in impaired eNOS dimer stability, increased superoxide and decreased NO biavailability in stably transfected HEK cells. Western blot analysis e.g. in aortic tissue proved the vascular specific overexpression of eNOS in C101A-eNOS-tg (149.7±8%, n=8, p<0.05) and eNOS-tg (228.7±15%, n=6, p<0.05) compared to transgene negative littermates. Superoxide levels were increased in C101A-eNOS-tg (214.1±30%, n=5, p<0.05) but not in eNOS-tg (89.4±8%, n=6; both vs. cont...