Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism

James M. Luther*, James V. Gainer, Laine J. Murphey, Chang Yu, Douglas E. Vaughan, Jason D. Morrow, Nancy J. Brown

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

This study tested the hypothesis that angiotensin promotes oxidative stress and inflammation in humans via aldosterone and the mineralocorticoid receptor. We measured the effect of intravenous aldosterone (0.7 μg/kg per hour for 10 hours followed by 0.9 μg/kg per hour for 4 hours) and vehicle in a randomized, double-blind crossover study in 11 sodium-restricted normotensive subjects. Aldosterone increased interleukin (IL)-6 (from 4.7±4.9 to 9.4±7.1 pg/mL; F=4.94; P=0.04) but did not affect blood pressure, serum potassium, or high-sensitivity C-reactive protein. We next conducted a randomized, double-blind, placebo-controlled, crossover study to measure the effect of 3-hour infusion of angiotensin II (2 ng/kg per minute) and norepinephrine (30 ng/kg per minute) on separate days after 2 weeks of placebo or spironolactone (50 mg per day) in 14 salt-replete normotensive subjects. Angiotensin II increased blood pressure (increase in systolic pressure: 13.7±7.5 and 15.2±9.4 mm Hg during placebo and spironolactone, respectively; P<0.001 for angiotensin II) and decreased renal plasma flow (-202±73 and -167±112 mL/min/1.73 kg/m; P<0.001 for angiotensin II effect) similarly during placebo and spironolactone. Spironolactone enhanced the aldosterone response to angiotensin II (increase of 17.0±10.6 versus 9.0±5.7 ng/dL; P=0.002). Angiotensin II transiently increased free plasma F2-isoprostanes similarly during placebo and spironolactone. Angiotensin II increased serum IL-6 concentrations during placebo (from 1.8±1.1 to 2.4±1.4 pg/mL; F=4.5; P=0.04) but spironolactone prevented this effect (F=6.4; P=0.03 for spironolactone effect). Norepinephrine increased blood pressure and F2-isoprostanes but not aldosterone or IL-6. Aldosterone increases IL-6 in humans. These data suggest that angiotensin II induces IL-6 through a mineralocorticoid receptor-dependent mechanism in humans. In contrast, angiotensin II-induced oxidative stress, as measured by F2-isoprostanes, is mineralocorticoid receptor independent and may be pressor dependent.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalHypertension
Volume48
Issue number6
DOIs
StatePublished - Dec 2006

Keywords

  • Aldosterone
  • Angiotensin II
  • F-isoprostanes
  • IL-6
  • Inflammation
  • Mineralocorticoid receptor
  • Oxidative
  • Spironolactone
  • Stress

ASJC Scopus subject areas

  • Internal Medicine

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