The Anti‐Contractile Effect of Perivascular Adipose Tissue is Maintained in Female Dahl Salt‐Sensitive Rats in Response to a High‐Fat Diet Despite Increases in Blood Pressure and Vascular Inflammation

Increased consumption of food high in saturated fat has been linked to the development of hypertension and related vascular dysfunction. Although the mechanism(s) by which a high‐fat diet (HFD) impacts blood pressure (BP) and vascular function remains unknown, immune cell activation and infiltration into the perivascular adipose tissue (PVAT) has been implicated in male experimental animals. There is limited data on the impact of HFD on BP and vascular function in females. Therefore, the goal of this study was to test the hypotheses that 1) HFD will increase BP and vascular immune cell infiltration and 2) PVAT will exacerbate HFD‐induced vascular dysfunction in female Dahl salt‐sensitive rats (DSS). To test these hypotheses, 5‐wk old female DSS were weaned onto a normal‐fat diet (NFD; 7.2% fat) or HFD (35% fat) and BP was measured by telemetry beginning at 10 wks of age. At 15 wks of age, thoracic aortic rings with PVAT intact or removed were mounted on pins for isometric myography, and cumulative concentration response curves to phenylephrine (PE) or acetylcholine (Ach) were generated (n=4–5). In separate rats, thoracic aortic T cells, macrophages, and cytokines were measured by flow cytometry. Rats maintained on HFD had significantly greater BP compared to rats on NFD (mmHg: 176 ± 8 HF vs 130 ± 4 NF, P<0.001; n=4). HFD‐induced increases in BP were associated with an increase in total aortic T cells (P=0.05), T cell activation (P=0.002), pro‐inflammatory Th17 cells (P=0.002), M1 macrophages (P=0.009), and TNFα + cells (P=0.06). There was no change in anti‐inflammatory T regulatory cells (P=0.67), although M2 macrophages (P <0.0001) and IL‐10 + cells (P=0.01) were lower following a HFD. HFD did not alter maximal relaxation to Ach (effect of diet P=0.15), increase in force generation to PE (effect of diet P=0.17), or sensitivity to either vasoactive agent when compared using a 2‐way ANOVA. However, the presence of PVAT increased maximal relaxation to Ach (% relaxation PVAT‐: NFD 178±15 vs. HFD 221±19; PVAT+: NFD 356±68 vs. HFD 489±84; effect of PVAT P<0.01) and attenuated PE‐induced constriction (% increase in force PVAT‐: NFD 80±11 vs. HFD 69±12; PVAT+: NFD 45±8 vs. HFD 26±2; effect of PVAT P<0.01). In conclusion, in contrast to what has been shown in male DSS following a HFD, vascular function is maintained in female DSS on a HFD despite increases in BP and vascular inflammation. In addition, PVAT enhances the vasodilatory capacity of the aorta in female DSS regardless of diet. Future studies will examine the mechanisms, such as oxidative stress, by which a HFD and PVAT modulate cardiovascular health in females. Support or Funding Information R01 HL127091‐01A1S1Type of Immune Cell Normal Fat High FatTotal T cells (CD3 + ) 19 ± 3, n=6 26 ± 2, n=7 *Activated T cells (CD3 + CD44 + ) 28 ± 4, n=6 46 ± 2, n=8 *M1 macrophages (CD11b/c + CD206 + TNFα + ) 1 ± 0.01, n=3 3 ± 0.4, n=4 *M2 macrophages (CD11b/c + CD206 + IL ‐ 10 + ) 1 ± 0.01, n=3 0.28 ± 0.05, n=4 *Effector Th17 cells (CD3 + CD4 + IL ‐ 17) 3.8 ± 0.9, n=6 11 ± 1, n=8 *T regulatory cells (CD3 + CD4 + FoxP3 + ) 3.8 ± 1.2, n=6 2.3 ± 0.5, n=8TNFα + cells 4 ± 0.9, n=3 8 ± 1, n=4 *IL‐10 + cells 6 ± 0.3, n=3 3 ± 0.5, n=4 *