Fig 1.
Plasma total homocysteine levels are elevated with the HM/LF diet.
Plasma levels of tHcy were measured in Sod1+/+, Sod1+/-, and Sod1-/- mice on either control or HM/LF diet (n = 11–15 mice per group). Values are mean ± SEM. *P < 0.05 compared to control diet.
Fig 2.
Vascular superoxide is increased with the HM/LF diet and SOD deficiency.
Representative confocal fluorescent images of DHE-stained carotid artery sections as a measure of superoxide from (A) Sod1+/+ mice fed control diet, (B) Sod1+/+ mice fed HM/LF diet, (C) Sod1-/- mice fed control diet, and (D) Sod1-/- mice fed HM/LF diet. (E) Carotid artery section from Sod1-/- mice fed HM/ LF diet preincubated with PEG-SOD prior to DHE staining. Scale bar = 50 μm. (F) DHE fluorescence relative to Sod1+/+ mice fed the control diet (n = 5–9 mice per group). Values are mean ± SEM. *P<0.01 compared to control diet; # P < 0.05 compared to Sod1+/+ on the same diet.
Fig 3.
SOD1 deficiency and the HM/LF diet produce an additive increase in endothelial dysfunction and induce a non-additive decrease in vasodilator responses to nitroprusside and papaverine.
Dilatation of cerebral arterioles to acetylcholine (10−6 M [A] or 10−5 M [B]), nitroprusside (10−8 M [C] or 10−7 M [D]), and papaverine (10−6 M [E] or 10−5 M [F] was measured in Sod1+/+, Sod1+/-, and Sod1-/- mice on either control or HM/LF diet (n = 7–10 mice per group). Values are mean ± SEM. *P<0.01 compared to control diet; # P < 0.05 compared to Sod1+/+ on the same diet.
Fig 4.
Graded effect of SOD1 deficiency on cerebral arteriolar cross-sectional area is augmented by the HM/LF diet.
Total cross-sectional area of vessel wall in cerebral arterioles in Sod1+/+, Sod1+/-, and Sod1-/- mice on either control or HM/LF diet (n = 7–10 mice per group). Values are mean ± SEM. *P < 0.05 compared to control diet; # P<0.05 compared to Sod1+/+ on the same diet.
Fig 5.
SOD1 deficiency and the HM/LF diet produce differential effects on smooth muscle and elastin components of the vessel wall.
Cross-sectional area of smooth muscle (A) and elastin (B) components in cerebral arterioles in Sod1+/+, Sod1+/-, and Sod1-/- mice on either control or HM/LF diet (n = 7–10 mice per group). Percent (%) volume density of smooth muscle (C) and elastin (D) components in cerebral arterioles (n = 7–10 mice per group). Values are mean ± SEM. *P<0.05 compared to control diet; # P < 0.05 compared to Sod1+/+ on the same diet.
Table 1.
Effect of hyperhomocysteinemia on cerebral arteriolar composition in SOD1-deficient mice.
Table 2.
Blood pressures, arterial blood gas parameters, and vascular mechanics.