The Role of T Cells in High Fat Diet Induced Hypertension and Vascular Dysfunction in Female Rats

Abstract

Hypertension is a leading risk factor for the development of cardiovascular disease (CVD) worldwide, affecting ~86 million adults in the United States alone. In general, the prevalence of hypertension is lower in premenopausal women than in age-matched men. Despite having lower risk than men, however, women represent more than half of all hypertension cases, and CVD is the leading cause of death in women worldwide. Women are also more likely than men to be obese and two-thirds of hypertension cases in the U.S. positively correlate with excessive weight gain due to the consumption of diets high in saturated fat. Dahl salt-sensitive rats (DSS) have traditionally been used to study salt-sensitive hypertension. However, previously, it has been shown that male DSS also exhibit a high fat diet (HFD)-induced increase in blood pressure (BP) at normal salt intake, which is attenuated by treatment with the lymphocyte inhibitor mycophenolate mofetil (MMF), suggesting a role for B and T cells in HF-induced hypertension in male animals. However, there is limited data on the role of HFD and T cell activation on BP in females. We hypothesized that HFD will promote hypertension and vascular dysfunction in female DSS and that these cardiovascular changes will be mediated by T cells. We demonstrate that female DSS are susceptible to HFD-induced hypertension and vascular T cell infiltration and activation similar to that of males. Since local inflammation in perivascular adipose tissue (PVAT) is linked to HFD-induced increases in BP and vascular dysfunction in males, we further investigated the impact of HFD on vascular function and the buffering capacity of PVAT in female DSS. HFD alone did not impair vascular function compared to normal fat diet (NFD) in female DSS. Interestingly, the buffering capacity of PVAT was also maintained in female DSS in response to a HFD despite increases in BP and vascular inflammation, likely due to overproduction of nitric oxide (NO). To directly assess the role of T cells on HFD-induced alterations of BP and vascular function in female DSS, we utilized female CD247-/- rats on the DSS background. HFD-induced increases in BP were completely abolished in CD247-/- . Further, the buffering capacity of PVAT was preserved in CD247-/- in response to a HFD. We conclude that T cells underlie the susceptibility of female DSS to HFD-induced hypertension. Further, vascular function and PVAT buffering capacity are maintained in female DSS despite fat-induced increases in BP and vascular inflammation, suggesting an adaptive response in the early stages of diet-induced obesity in which nitric oxide (NO) may play a key role.