Renal T cell infiltration occurs despite attenuation of development of hypertension with hydralazine in Envigo's female Dahl rat maintained on a low-Na + diet

Am J Physiol Renal Physiol. 2019 Sep 1;317(3):F572-F583. doi: 10.1152/ajprenal.00512.2018. Epub 2019 Jun 26.

Abstract

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg-1·day-1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group (n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group (n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.

Keywords: CD25; activated T cells; immune system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Arterial Pressure* / drug effects
  • Diet, Sodium-Restricted*
  • Disease Models, Animal
  • Female
  • Heart Rate
  • Hydralazine / pharmacology
  • Hypertension / immunology
  • Hypertension / physiopathology
  • Hypertension / prevention & control*
  • Kidney / drug effects
  • Kidney / immunology*
  • Lymph Nodes / immunology
  • Rats, Inbred Dahl
  • Spleen / immunology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Vasodilator Agents / pharmacology

Substances

  • Antihypertensive Agents
  • Vasodilator Agents
  • Hydralazine