Abstract
Evidence supports a sex difference in the impact of a high-fat diet (HFD) on cardiovascular outcomes, with male experimental animals exhibiting greater increases in blood pressure (BP) than female experimental animals. The immune system has been implicated in HFD-induced increases in BP, and there is a sex difference in T-cell activation in hypertension. The goal of this study was to determine the impact of HFD on BP and aortic and renal T cell profiles in male and female Dahl salt-sensitive (DSS) rats. We hypothesized that male DSS rats would have greater increases in BP and T cell infiltration in response to a HFD compared with female DSS rats. BP was measured by tail-cuff plethysmography, and aortic and renal T cells were assessed by flow cytometric analysis in male and female DSS rats on a normal-fat diet (NFD) or HFD from 12 to 16 wk of age. Four weeks of HFD increased BP in male and female DSS rats to a similar degree. Increases in BP were accompanied by increased percentages of CD4+ T cells and T helper (Th)17 cells in both sexes, although male rats had more proinflammatory T cells. Percentages of renal CD3+ and CD4+ T cells as well as Th17 cells were increased in both sexes by the HFD, although the increase in CD3+ T cells was greater in male rats. HFD also decreased the percentage of aortic and renal regulatory T cells in both sexes, although female rats maintained more regulatory T cells than male rats regardless of diet. In conclusion, both male and female DSS rats exhibit BP sensitivity to a HFD; however, the mechanisms mediating HFD-induced increases in BP may be distinct as male rats exhibit greater increases in the percentage of proinflammatory T cells than female rats.NEW & NOTEWORTHY Our study demonstrates that male and female Dahl salt-sensitive rats exhibit similar increases in blood pressure to a high-fat diet and an increase in aortic and renal T cells. These results are in contrast to studies showing that female rats remain normotensive and/or upregulate regulatory T cells in response to hypertensive stimuli compared with male rats. Our data suggest that a 4-wk high-fat diet has sex-specific effects on the T cell profile in Dahl salt-sensitive rats.
Highlights
Two-thirds of hypertension cases in the United States are positively correlated with excessive weight gain [22], and recent data from the National Health and Examination Survey indicate that the prevalence of hypertension increases with body mass index [49]
Based on studies of angiotensin II-induced hypertension [19, 29, 56] and spontaneously hypertensive rats (SHRs) [67, 70] indicating sex differences in T cell activation in hypertension, where hypertensive male animals exhibit a more proinflammatory T cell profile compared with female animals, the present study was designed to test the hypothesis that male Dahl salt-sensitive (DSS) rats will have greater increases in blood pressure (BP) and T cell infiltration in the vasculature and kidney in response to a high-fat diet (HFD) compared with female DSS rats
Total food intake was less in rats of both sexes on a HFD compared with a normal-fat diet (NFD) at baseline and at week 4 of treatment, total fat intake was significantly greater in rats on a HFD compared with NFD in both sexes
Summary
Two-thirds of hypertension cases in the United States are positively correlated with excessive weight gain [22], and recent data from the National Health and Examination Survey indicate that the prevalence of hypertension increases with body mass index [49] In both humans and animal models of hypertension, dietary factors such as saturated fat, cholesterol, and carbohydrates have a profound influence on blood pressure (BP) control [21, 59, 71]. Hypertensive male DSS rats exhibit an increase in aortic inflammation and CD8ϩ T cell infiltration compared with normotensive control rats Taken together, these findings support a critical role for immune cells in HFD-induced hypertension in male DSS rats; female rats were not studied. Based on studies of angiotensin II-induced hypertension [19, 29, 56] and spontaneously hypertensive rats (SHRs) [67, 70] indicating sex differences in T cell activation in hypertension, where hypertensive male animals exhibit a more proinflammatory T cell profile compared with female animals, the present study was designed to test the hypothesis that male DSS rats will have greater increases in BP and T cell infiltration in the vasculature and kidney in response to a HFD compared with female DSS rats
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