Greater T Regulatory Cells in Females Attenuate DOCA-Salt-Induced Increases in Blood Pressure Versus Males

Hypertension. 2020 Jun;75(6):1615-1623. doi: 10.1161/HYPERTENSIONAHA.119.14089. Epub 2020 Apr 27.

Abstract

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.

Keywords: blood pressure; cardiovascular disease; hypertension; inflammation; kidney.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / immunology
  • Cardiometabolic Risk Factors
  • Cell Count / methods
  • Desoxycorticosterone Acetate / pharmacology*
  • Female
  • Flavoring Agents / pharmacology
  • Hypertension* / immunology
  • Hypertension* / physiopathology
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Kidney* / immunology
  • Kidney* / pathology
  • Male
  • Mineralocorticoids / pharmacology
  • Protective Factors
  • Rats
  • Sex Factors*
  • Sodium Chloride, Dietary / pharmacology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome

Substances

  • Flavoring Agents
  • Interleukin-2 Receptor alpha Subunit
  • Mineralocorticoids
  • Sodium Chloride, Dietary
  • Desoxycorticosterone Acetate