Female Dahl, but Not SS13^BN, Rats Are Susceptible to High-Fat Diet-Induced Hypertension

Immune system activation has been implicated in high-fat diet (HFD)-induced elevations in blood pressure (BP) in female Dahl rats. The goal of the current study was to determine the impact of a 10-week HFD on BP, aortic T cell profiles, and vascular function in female Dahl rats and their genetic controls, consomic SS13^BN rats. We hypothesized that female Dahl rats would have greater increases in BP, aortic T cell infiltration, and vascular dysfunction in response to a HFD compared to SS13^BN rats. Rats were randomized to normal fat diet (NFD) or HFD at 5 weeks of age. Radio-telemeters were implanted at 8 weeks of age and BP was continuously recorded to 15 weeks of age. Aortic T cell profiles were measured by flow cytometry, vascular function by wire myography, and an adipose tissue array was conducted to assess adipokines. While female Dahl rats exhibited HFD-induced hypertension, BP was not different between NFD- and HFD-fed SS13^BN controls despite similar caloric intake and increases in body weight in both strains. HFD increased percentages of inflammatory CD4⁺ T cells and T helper 17 cells (Th17) and decreased percentages of anti-inflammatory regulatory T cells (Tregs) in the aorta regardless of rat strain, although SS13^BN rats had a less pro-inflammatory immune profile than Dahl rats. Moreover, perivascular adipose tissue (PVAT) attenuated phenylephrine-mediated aortic contraction to a greater extent in SS13^BN rats than in Dahl rats fed an HFD. Of the 30 adipokines assessed, visceral adipose tissue expression of the anti-inflammatory adipokines lipocalin-2 and TIMP-1 was reduced in both strains following HFD treatment, with a greater magnitude of decrease in SS13^BN rats. Overall, these data indicate that genetic background influences susceptibility to HFD-induced hypertension in females, with enhanced PVAT-mediated regulation of vascular function and a less pro-inflammatory milieu in SS13^BN rats.