Female Dahl, but Not SS13BN, 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.