Tgsod2

Isometric tension studies were performed on 2 mm mouse aortic rings dissected free of perivascular fat from C57B/6J, mCAT, tg^SOD2 and CypD^−/− mice (Jackson Lab). Studies were performed in a horizontal wire myograph (DMT, Aarhus, Denmark, models 610M and 620M) containing physiological salt solution with the composition of 118 mM NaCl, 4.7 mM KCl, 1.2 mM MgSO₄, 1.2 mM KH₂PO₄, 25 mM NaHCO₃, 11 mM glucose, and 1.8 mM CaCl₂. The isometric tone of each vessel was recorded using LabChart Pro v7.3.7 (AD Instruments, Australia). The aortic rings were equilibrated over a 2-hour period by heating and stretching the vessels to an optimal baseline tension of 36 millinewtons before contracting them with three cycles of 60 mM KCl physiological saline solution. Endothelium-dependent and independent vascular relaxation was tested following pre-constriction with 1uM phenylephrine. Once the vessels reached a steady state contraction, increasing concentrations of acetylcholine were administered, and the response to each concentration of drug was recorded.

Hypertension was induced by Ang II infusion (0.7 mg/kg/day, Sigma A6402) in 2–3 months old male mice as described previously ^{22 (link)} using mCAT (Stock# 016197), Tg^{SOD2 23} and CypD^−/− (Stock# 022308) mice which have C57Bl/6J genetic background (Jackson Labs). In some experiments, six days after saline or Ang II minipump placement, C57Bl/6J mice received a second minipump for infusion with saline as vehicle or the CypD inhibitor SFA (i.p. 10 mg/kg/day). In order to test the pro-hypertensive role of IL17A some mice were infused with recombinant mouse IL17A (i.p. 1.5 μg/day, Ebioscience, 14-8171). The role of TNFα was tested by i.p. treatment with TNFα blocker Etanercept (i.p. 0.2 mg/day, Amgen Inc.). Blood pressure was monitored by the telemetry and tail cuff methods as previously described.^{24 (link), 25 (link)}