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.

Obesity is a common metabolic disorder that has become a widespread epidemic in several countries. Sex and gender disparities in the prevalence of cardiovascular disease (CVD) have been well documented with premenopausal women having a lower incidence of CVD than age-matched men. However, women are more likely than men to suffer from obesity, which can predispose them to a greater risk of CVD. The mechanisms underlying high-fat diet (HFD)-or obesity-induced hypertension are not well defined, although immune system activation and inflammation have been implicated in several studies. Further, the sex of the subject can have a profound influence on the immune response to hypertensive stimuli. Therefore, the purpose of this review is to examine the effects of sex and gender on the role of the immune system in HFD-induced hypertension and vascular dysfunction.

BackgroundMortality rate for breast cancer is higher among African American (AA) women than for women of other racial/ethnic groups. Obesity, also higher among AA women, may increase the risk of breast cancer development and recurrence. Lifestyle factors such as healthy nutrition can reduce the rate of obesity and breast cancer. This study examined the determinants of adherence to nutrition-related cancer prevention guidelines among AA breast cancer survivors.MethodsAA breast cancer survivors (n=240) were recruited from a breast cancer support group to complete a lifestyle assessment tool for this cross-sectional study. Chi-square test and ordinal logistic regression analysis were used to examine the relationship between adherence to nutrition-related cancer prevention guidelines and potential predictors of adherence.ResultsMajority of the survivors met the guideline for red and processed meat (n=191, 83.4%), but did not meet the guideline for fruits and vegetables (n=189, 80.4%). For survivors with annual household incomes < $25,000, the odds of meeting or partially meeting the guideline for fruits and vegetables was 75.4% less than for participants with incomes > $50,000 (OR= 0.25, 95% CI: 0.08, 0.80). Poor physical functioning (OR= 38.48, 95% CI: 2.26, 656.58), sleep disturbances (OR= 60.84, 95% CI: 1.61, 2296.02), and income > $50,000 (OR= 51.02, 95% CI: 1.13, 2311.70) were associated with meeting the guideline for red and processed meat.ConclusionsMany AA breast cancer survivors are not meeting the nutrition-related cancer prevention guidelines. For this population, more interventions that enhance access to and consumption of healthy diets are needed.

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11–14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.

Background Chronic ingestion of a high‐fat diet (HFD) is pro‐inflammatory and has been linked to the development of hypertension. The NLRP3 inflammasome contributes to adipose tissue inflammation with a chronic HFD in males, yet the role in blood pressure (BP) control is unknown. Interestingly, there is increasing evidence that females are highly susceptible to cardiovascular complications following a chronic HFD. The Dahl rat is a model of HFD‐induced hypertension and adiposity. The goal of the current study was to test the hypothesis that NLRP3 contributes to HFD‐induced increases in BP in female Dahl rats. Methods 5‐week‐old female wildtype (WT; n=4‐8) and NLRP3 knockout (KO; n=3‐6) Dahl rats were randomized to either a control normal fat diet (NFD; 7.2% calories from fat) or high fat diet (HFD; 36% of calories from fat). Body weights were measured weekly. At 15 weeks of age, body fat mass was measured via nuclear magnetic resonance. Rats were then implanted with telemetry devices and BP was measured from 16‐17 weeks of age. Results Following 10 weeks of treatment with HFD, body fat percentage increased in female WT Dahl rats, however HFD‐induced increases in body fat were attenuated in NLRP3 KO rats (Table, PInteraction=0.04, PDiet=0.01, Pgenotype<0.0001). Despite significant differences in body fat, all groups had similar body weights following 10 weeks of dietary treatment (PInteraction=0.56, PDiet=0.24, Pgenotype=0.09). We confirmed that chronic consumption of HFD increased MAP in female WT Dahl rats vs rats on NFD. HFD‐induced increases in MAP were attenuated in NLRP3 KO rats (PInteraction=0.02, PDiet=0.001, Pgenotype=0.28). Discussion Our findings indicate that NLRP3 contributes to chronic HFD‐induced increases in body fat and MAP in female Dahl rats. Most Americans eat more than the recommended amount of saturated fat. Since decreasing the intake of saturated fats is difficult, more basic science research like this project is necessary to understand the mechanisms through which females on a HFD have compromised cardiovascular health.

Prenatal, perinatal, and adulthood exposure to chronic intermittent hypoxia (IH) increases blood pressure in rodents. Males exposed to chronic IH have higher blood pressure vs females. However, it is unknown if this same sex difference exists with acute perinatal IH. We tested the hypothesis that acute perinatal IH increases baseline blood pressure and enhances sensitivity to angiotensin II-induced hypertension in male Sprague Dawley rats. Male and female pups were randomized to control (room air) or IH (10 minutes of ~10% O2 three times/day) for the first 8 days of life. IH decreased oxygen saturation, confirmed via pulse oximeter. Pups were weaned at postnatal day 21. Blood pressure was measured via telemetry beginning at 14 weeks of age and analyzed separated into light and dark phase to assess circadian rhythm. Osmotic mini-pumps to deliver angiotensin II were implanted at 15 weeks of age. Perinatal IH exposure did not alter baseline blood pressure. One week of Ang II treatment increased blood pressure in the light and dark periods in males exposed to IH vs control; there was no effect in females. Blood pressure among groups was comparable following 2 weeks of angiotensin II infusion. Perinatal IH did not change circadian rhythm. Following angiotensin II treatment, indices of renal injury were measured. Perinatal IH did not alter kidney size, structure, nephron number or creatinine clearance. These data indicate that acute perinatal IH enhances early angiotensin II-induced hypertension in males, independent of nephron loss or decreases in body weight or kidney function.

Diets high in saturated fats are increasingly linked to the development of hypertension, yet the mechanisms by which high saturated fat diet (HFD) increases blood pressure remain unclear. Although young women are typically protected from hypertension relative to age-matched men, recent studies suggest that the cardiovascular protection in young women is compromised by chronic consumption of a HFD. We hypothesize that chronic HFD treatment causes a greater increase in blood pressure in females via sex-specific activation and recruitment of T cells and adipocyte expansion. Male and female Dahl rats (n=4-5) were placed on HFD at 8 wks of age. After 4 wks of HFD, blood pressure (BP) significantly increased in male and female Dahl rats to a comparable degree. Although BP continued to increase over the course of 10 wks of HFD treatment, female rats have a greater increases in BP (~40 mmHg increase in BP) after 10 weeks of HFD vs. males (~20 mmHg increase in BP). Fat pad weight and adipose tissue expansion increased in WT rats of both sexes following 10 wks of HFD treatment, yet females exhibited greater increases in fat pad weight and adipose tissue expansion vs. males. To determine whether T cells contributes to sex differences in BP elevation in Dahl rats fed HFD, we utilized Dahl rats lacking CD247 which encodes the T cell receptor CD3 chain that is required for T cell signaling. 10 wks of HF feeding did not change BP in either sex of Dahl CD247 KO rats. There were attenuated increases in fat pad weight and adipocyte expansion in Dahl CD247 KO rats and females exhibited more pronounced attenuations than males. Flow cytometric analysis revealed that HFD decreased Tregs and increased Th17 cells in both sexes of Dahl WT rats and females on HFD had the most pro-inflammatory T cell profile indicted by the Th17 cells:Tregs ratio. Our data suggest that greater adipocyte expansion with a HFD feeding in female Dahl rats vs. male might result in greater recruitment and activation of pro-inflammatory T cells and larger increases in BP.

Background Diets high in saturated fats promote inflammation and are linked to the development of many cardiovascular diseases (CVD). Young females are typically protected from CVD vs males. However, epidemiological and basic science studies suggest that the cardiovascular protection in females is compromised by a high fat diet (HFD). Little is known regarding the impact of a HFD on T cells in males vs. females. Therefore, the current study tested the hypothesis that a HFD results in a more pro‐inflammatory T cell profile in females vs. males. Methods 26‐day‐old male and female Sprague Dawley rats (n=3–5 per group) were randomized to a control (Ctrl; 7.2% calories from fat) or HFD (36% of calories from fat) for 10 weeks. 24 hour food consumption was measured every 3 weeks. Body weights were measured weekly. At the end of the 10 week treatment, body fat composition was measured via NMR. Rats were euthanized and spleen were isolated for flow cytometric analysis of Pan T cells (CD3+), CD4+ T cells (CD3+CD4+), and T regulatory cells (Tregs; CD3+CD4+FOXP3+). Results Throughout the treatment, rats on HFD consumed more kcal from fat vs Ctrls (P<0.05). There were no differences in body weight between Ctrl and HFD rats of the same sex (P>0.05 at each time point), although males were heavier than females at all time points (P<0.05), Table 1. Following 10 weeks of treatment, HFD increased body fat percentage in both sexes vs Ctrl, (PDiet=0.01). Increases in body fat were similarly in both sexes (PSex=0.33; Pinteraction=0.37). At end of treatment, all groups had similar percentages of splenic CD3+ cells (Pdiet=0.27; Psex=0.14; Pinteraction=0.41). However, rats on a HFD had more CD4+ T cells vs Ctrl (PDiet=0.006). Moreover, females had more CD4+ T cells vs males (PSex=0.002; Pinteraction=0.09). HF females had the most splenic Tregs vs all groups (PDiet=0.28, PSex=0.09, PInteraction=0.007. Discussion This dietary model allows for investigation of the effects of a HFD on body composition and T cell count independent of obesity. Evidence in the literature suggests high anti‐inflammatory Tregs in female rats contributes to cardiovascular protection and decrease in renal Tregs compromises this protection. Thus, the increase in splenic Tregs in females on a HFD may show a compensatory increase to counteract the decreased renal Tregs observed in the literature. Future studies will test this hypothesis. Data following 0 and 10 weeks of dietary treatment expressed as means ± SEM. Assay Weeks of treatment Population Ctrl F HF‐F Ctrl‐M HF‐M Body weight (g) 0 73.25 ± 0.48 70 ± 1.05 83.2 ± 2.13 80.2 ± 1.07 10 254 ± 8.57 242.4 ± 11.05 411 ± 11.79 410.8 ± 13.72 Body fat percentage 10 7.94 ± 0.49 11.35 ± 1.23 7.84 ± 1.69 10.18 ± 0.82 Splenic T cells 10 CD3 21.5 ± 1.55 20.96 ± 2.02 25.9 ± 2.3 22.28 ± 0.65 CD4 73.48 ± 1.38 77.36 ± 2.85 58.8 ± 2.91 72.23 ± 2.44 Tregs 6.05 ± 0.31 8.47 ± 0.79 7.55 ± 0.92 5.63 ± 0.32