Fig. 8 |. IL-17 suppresses NO production via ROCK, and ROCK inhibition ameliorates the neurovascular and cognitive dysfunction of HSD.

a,b, IL-17 induces eNOS phosphorylation at Thr⁴⁹⁵ (^⋆P < 0.0001 vs. vehicle 0 IL-17, n = 3−6 independent experiments; one-way ANOVA and Tukey’s test). c, IL-17 attenuates the increase in NO induced by ACh in mouse brain endothelial cell cultures. The attenuation by IL-17 of the ACh-induced NO increase is prevented by coadministration of Y27632 (5 μM), but not by inhibitors of ERK (PD98059; 10 μM) or PKC (Go6976; 1 μM). NO increase: ^⋆P = 0.0156, treatment: ^⋆P < 0.0001; n = 3−6 independent experiments per group; repeated-measures two-way ANOVA and Tukey’s test). d, Systemic administration of Y27632 does not affect the elevation in plasma IL-17 induced by 12 weeks of HSD (diet: ^⋆P < 0.0001, treatment: P = 0.5559, ND Veh and Y27632 n = 9 and 5 mice per group, HSD Veh and Y27632 n = 7 and 9 mice per group; two-way ANOVA and Tukey’s test). e, MAP is also not affected (ND Veh and Y27632 n = 6 and 5 mice per group, HSD Veh and Y27632 n = 6 and 8 mice per/group). f, Y27632 prevents the attenuation of the CBF response to ACh induced by HSD (diet: ^⋆P < 0.0001, treatment: ^⋆P = 0.0364, ND Veh and Y27632 n = 6 mice per group, HSD Veh and Y27632 n = 6 and 8 mice per group; two-way ANOVA and Tukey’s test). g, Y27632 prevents the behavioral dysfunction induced by HSD (diet: ^⋆P = 0.0486, ND Veh and Y27632 n = 11 and 10 mice per group, HSD Veh and Y27632 n = 11 and 11 mice per group; two-way ANOVA and Tukey’s test). h, Y27632 blocks the increase in eNOS phosphorylation induced by HSD (P = 0.5761 vs. ND; microvessels isolated from 5 ND and 9 HSD mice per group; unpaired t test, two-tailed). Data were derived from 3 independent experiments and are expressed as mean ± s.e.m. Immunoblots in a and h are cropped; full gel pictures for immunoblots are shown in Supplementary Figs. 13 and 14.