FIGURE 6.

Effect of VEGF^KD on circulating and urine VEGF-A and NO in diabetic and eNOS^−/−:VEGF^KD mice. (A) plasma VEGF-A is similarly elevated in eNOS^−/−:VEGF^KD mice (red bars) irrespectively of VEGF^KD , as compared to non-diabetic eNOS intact mice (VEGF^KD − dox, white bar) (****, p =<0.0001) or VEGF^KD + dox mice (gray bar) (*, p < 0.005); in diabetic mice VEGF^KD (DM-VEGF^KD + dox, blue bar) significantly decreases circulating VEGF-A (**, p = 0.0013), but all diabetic mice have plasma VEGF-A >2-fold higher than non-diabetic mice with intact eNOS (VEGF^KD , white/gray bars) (****, p < 0.0001 and ***, p = 0.0006). (B) Urine VEGF-A: podocyte VEGF^KD does not alter VEGF-A excretion in eNOS^−/−:VEGF^KD (red bars) or diabetic mice (blue bars); VEGF^KD significantly inhibits VEGF-A excretion in non-diabetic mice (VEGF^KD + dox, gray bar) (**, p = 0.0043). (C) Plasma NO: podocyte VEGF^KD (+ dox) does not significantly alter plasma NO in any experimental group; plasma NO is lower in eNOS^−/−:VEGF^KD (red bars) than diabetic (blue bars) (**, p = 0.001 and ***, p = 0.0009) and non-diabetic mice with intact eNOS (white bar) (*, p = 0.047); plasma NO is higher in diabetic (DM-VEGF^KD − dox, hatched blue bar) than in non-diabetic mice (VEGF^KD − dox, white bar) (*, p = 0.015) and VEGF^KD abrogates this change (DM-VEGF^KD + dox, blue bar). (D) Urine NO: VEGF^KD increases NO excretion in eNOS^−/−:VEGF^KD + dox mice (*, p = 0.0272, red bar); all diabetic mice (blue bars) have several fold higher NO excretion than non-diabetic mice (white/gray bars), irrespectively of VEGF^KD .