Sex and gender differences in hypertensive kidney injury

Abstract

Hypertension is a complex, multifaceted disorder, affecting ~1 in 3 adults in the United States. Although hypertension occurs in both men and women, there are distinct sex differences in the way in which they develop hypertension, with women having a lower incidence of hypertension until the sixth decade of life. Despite observed sex differences in hypertension, little is known about the molecular mechanisms underlying the development of hypertension in females, primarily because of their underrepresentation in both clinical and experimental animal studies. The first goal of this review is to provide a concise overview of the participation of women in clinical trials, including a discussion of the importance of including females in basic science research, as recently mandated by the National Institutes of Health. The remaining portion of the review is dedicated to identifying clinical and experimental animal studies that concentrate on gender and sex differences in hypertensive kidney disease, ending with a proposed role for T cells in mediating sex differences in blood pressure.

Keywords: T cells; T regulatory cells; angiotensin type 2 receptor; blood pressure; renin-angiotensin system.

Fig. 1.

Renal T cells were measured by analytical flow cytometry of single-cell suspensions of kidneys from 5-wk-old (n = 4) and 13-wk-old (n = 6–8) male and female SHR as previously described (73, 74); these data have not been previously published. Tregs are expressed as CD3⁺CD4⁺FoxP3⁺ cells; Th17 cells are expressed as CD3⁺CD4⁺RORγ⁺ cells. All data are expressed as means ± SE, and data were compared using a two-way ANOVA (factor 1, sex; factor 2, age; GraphPad Prism; GraphPad Software, La Jolla, CA). FoxP3, forkhead box P3; ROR, retinoic acid-related orphan receptor.