Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells

Am J Physiol Renal Physiol. 2020 Aug 1;319(2):F192-F201. doi: 10.1152/ajprenal.00228.2020. Epub 2020 Jun 29.

Abstract

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.

Keywords: Nω-nitro-l-arginine methyl ester; angiotensin II; blood pressure; norepinephrine.

Publication types

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

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Hypertension / physiopathology*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Function Tests
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Rats, Sprague-Dawley
  • T-Lymphocytes, Regulatory / drug effects*

Substances

  • Enzyme Inhibitors
  • Angiotensin II
  • Nitric Oxide Synthase