Mitochondrial Oxidative Stress and Hypertension

Hypertension was induced by angiotensin II (490 ng/kg/min) as described previously 25 (link) using either C57Bl/6 or mice transgenic for human SOD2 (tg^SOD2 mice). In addition, mice received a separate minipump for co-infusion of either TEMPOL, mitoTEMPO or vehicle as described in the figure legends. In other animals, mitoTEMPO treatment was started seven days after saline or angiotensin II minipump placement. Blood pressure was monitored using either the tail cuff method or telemetry as previously described 26 (link), 27 (link). Following 14 days of angiotensin II infusion the animals were sacrificed by CO₂ inhalation and aortas were extracted for the analysis of nitric oxide and O₂^∸ production, and endothelial functions. DOCA-salt induced hypertension was induced as described previously 28 (link) using C57Bl/6 mice. Ten days after surgery the mice were implanted with osmotic pumps containing saline or mitoTEMPO (0.7 mg/kg/day). Seventeen days after surgery the animals were sacrificed by CO₂ inhalation and segments of mouse aorta were used for analysis of vascular nitric oxide and O₂^∸ production. Endothelium-dependent vasodilatation was analyzed in isolated 3-mm aortic segments in organ chambers as we have previously described 27 (link).