Role of vascular superoxide in hypertension

Prior studies indicate that superoxide (O 2 •− ) is important in modulation of blood pressure, but have not specifically identified the organ or tissue involved. We created mice with loxP sites flanking either of the extracellular superoxide dismutase (SOD3) or the p22 phox genes. 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 or p22 phox . Deletion of SOD3 increased vascular O 2 •− as detected by electron spin resonance and dihydroethidium oxidation measured by HPLC both at baseline and after 14 days of angiotensin II infusion. Endothelium dependent vasodilatation was modestly impaired after angiotensin II infusion in mice lacking vascular SOD3. Despite increased vascular O 2 •− , hypertension was not increased by deletion of SOD3. Deletion of p22 phox in the vascular smooth muscle had no effect on baseline blood pressure, however blunted the hypertensive response to angiotensin II (p22 phoxloxP/loxP : 151 ± 3 mmHg; p22 phoxloxP/loxP × tg cre/smmhc : 123 ± 9 mmHg; P = 0.00125). These data indicate that increased vascular ROS are necessary but not sufficient to cause an elevation in blood pressure. Moreover differences in the location and species of ROS induced by deletion of SOD3 and p22phox could explain variations in hypertension caused by these genetic manipulations.