Figure 3.

PVAT-dependent endothelial function is altered in HBK mice. Vascular reactivity studies in the thoracic aorta of HBK and flox mice were assessed with acetylcholine (ACh)-induced vasorelaxation in the absence and presence of PVAT (A), E_max in the absence and presence of PVAT in flox and HBK mice (B), ACh EC₅₀ in the absence and presence of PVAT in flox and HBK mice (C), phenylephrine (PE)-induced vasoconstriction curves in the absence and presence of PVAT (D), PE-induced responses assessed by AUC in flox and HBK mice in the presence and absence of PVAT (E), and PE EC₅₀ in the absence and presence of PVAT in flox and HBK mice (F). Sensitivity (−log EC₅₀) and maximal effect (E_max) were determined in response to agonists. Two-way ANOVA was used to compare effects of PVAT and genotype with Tukey’s post hoc test (n = 6 or 12, *P < 0.05). Refer to Table 4 for values of ACh, SNP, PE, and KCl curves and statistical analysis. Significant two-way ANOVA results are included in graphs. PVAT had a significant effect on ACh E_max (A and B), ACh EC₅₀ (A and C), PE AUC (E), and PE EC₅₀ (D and F). There was a significant effect of genotype on PE AUC (E). Symbols indicate statistically significant differences (P < 0.05) for post hoc tests showing differences within genotypes with (+) and without (−)PVAT. †P < 0.05 Flox + PVAT vs. Flox; *P < 0.05 HBK + PVAT vs. HBK. AUC, area under the curve; HBK, hepatocyte-specific Bmal1 knockout; PE, phenylephrine; PVAT, perivascular adipose tissue; SNP, sodium nitroprusside.