T cell knockout attenuates HFD-induced increases in blood pressure in female and male Dahl rats

Abstract

Increased body weight is associated with a higher incidence of hypertension in humans. Pre-clinical evidence shows that a high-fat diet (HFD) promotes hypertension. While T cells have been implicated in hypertension, the contribution of T cells to HFD-induced increases in blood pressure (BP) remains unknown. We tested the hypothesis that T cells mediate HFD-induced increases in BP in female and male Dahl rats. Female and male wildtype (WT) Dahl rats were randomized to a normal-fat diet (0.16% kcal from fat) or HFD (59% kcal from fat) from 5 to 15 weeks of age. Aortic and renal T cells were measured by flow cytometry. Additional female and male WT and CD247 (CD3ζ-chain) knockout (KO) Dahl rats were placed on a HFD from 5 to 15 weeks of age. Body weight and fat and lean mass were measured throughout, and BP was measured by telemetry throughout the last five weeks of treatment. At 15 weeks of age, rats were euthanized, and adipose tissues were weighed. HFD increased pro-inflammatory T cells and decreased anti-inflammatory T regulatory cells in the aorta and kidney in both sexes, indicating an increase in the pro-inflammatory status. HFD increased BP comparably in females and males, and the change in BP in response to HFD was blunted in CD247 KO rats of both sexes. The lower BP in CD247 KO rats was independent of changes in body weight or total fat mass. Our findings suggest that T cells contribute to HFD-induced hypertension in both sexes independent of changes in adiposity.

Keywords: inflammation; mean arterial pressure; sex; telemetry.