While it has been known since the 1940s that men have greater increases in blood pressure (BP) compared with women, there have been intense efforts more recently to increase awareness that women are also at risk for developing hypertension and that cardiovascular diseases (CVDs) are the leading causes of death among both men and women in the United States. With the release of the 2017 Hypertension Clinical Guidelines, 46% of adults in the United States are now classified as hypertensive, and hypertension is the primary modifiable risk factor for the development of CVD. This increase in the prevalence of hypertension is reflected in an increase in prevalence among both men and women across all demographics, although there were greater increases in the prevalence of hypertension among men compared with women. As a result, the well-established gender difference in the prevalence of hypertension is even more pronounced and now extends into the sixth decade of life. The goals of this review are to (i) review the historical clinical trial data and hypertension guidelines from the perspective of both genders and then (ii) review the role of the renin–angiotensin system and T-cell activation in contributing to sex differences in BP control.

Although numerous clinical and experimental studies have clearly identified a sexual dimorphism in blood pressure control, the mechanism(s) underlying gender differences in blood pressure remain unclear. Over the past two decades, numerous laboratories have utilized the spontaneously hypertensive rats (SHR) as an experimental model of essential hypertension to increase our understanding of the mechanisms regulating blood pressure in males and females. Previous work by our group and others have implicated that differential regulation of adrenergic receptors, the renin–angiotensin system, oxidative stress, nitric oxide bioavailability and immune cells contribute to sex differences in blood pressure control in SHR. The purpose of this review is to summarize previous findings to date regarding the mechanisms of blood pressure control in male versus female SHR.

Hypertension is the most common risk factor for cardiovascular disease, causing over 18 million deaths a year. Although the mechanisms controlling blood pressure (BP) in either sex remain largely unknown, T cells play a critical role in the development of hypertension. Further evidence supports a role for the immune system in contributing to sex differences in hypertension. The goal of the current study was to first, determine the impact of sex on the renal T-cell profiles in DOCA-salt hypertensive males and females and second, test the hypothesis that greater numbers of T regulatory cells (Tregs) in females protect against DOCA-salt–induced increases in BP and kidney injury. Male rats displayed greater increases in BP than females following 3 weeks of DOCA-salt treatment, although increases in renal injury were comparable between the sexes. DOCA-salt treatment resulted in an increase in proinflammatory T cells in both sexes; however, females had more anti-inflammatory Tregs than males. Additional male and female DOCA-salt rats were treated with anti-CD25 to decrease Tregs. Decreasing Tregs significantly increased BP only in females, thereby abolishing the sex difference in the BP response to DOCA-salt. This data supports the hypothesis that Tregs protect against the development of hypertension and are particularly important for the control of BP in females.

Obesity is a potent predictor of cardiovascular disease and associated risk factors, including hypertension. Systemic inflammation has been suggested by a number of studies to be an important link between excess adiposity and hypertension, yet the majority of the studies have been conducted exclusively in males. This is problematic since women represent ∼53% of hypertensive cases and are more likely than men to be obese. There is a growing body of literature supporting a central role for immune cell activation in numerous experimental models of hypertension, and both the sex of the subject and the sex of the T cell have been shown to impact blood pressure (BP) responses to hypertensive stimuli. Moreover, sex steroid hormones play an important role in energy homeostasis, as well as in the regulation of immune responses; estrogen, in particular, has a well-known impact on both cardiovascular and metabolic disorders. Therefore, the purpose of this review is to examine whether sex or sex hormones regulate the role of the immune system in the development of hypertension and related vascular dysfunction in response to metabolic changes and stimuli, including a high-fat diet.

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.