Interleukin 6 knockout prevents angiotensin II hypertension: Role of renal vasoconstriction and janus kinase 2/signal transducer and activator of transcription 3 activation

Michael W. Brands, Amy K.L. Banes-Berceli, Edward W. Inscho, Hind Al-Azawi, Ashlyn J. Allen, Hicham Labazi

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Chronic angiotensin II (Ang II) infusion stimulates interleukin (IL) 6 release, and we and others have shown that preventing the increase in IL-6 significantly attenuates Ang II hypertension. This study measured renal blood flow (RBF) chronically, using Transonic flow probes in wild-type (WT) and IL-6 knockout (KO) mice, to determine the role of RBF regulation in that response. Ang II infusion at 200, 800, and 3600 ng/kg per minute caused a dose-dependent decrease in RBF in WT mice, and the response at 800 ng/kg per minute was compared between WT and IL-6 KO mice. Ang II infusion increased plasma IL-6 concentration in WT mice and increased mean arterial pressure (19 h/d with telemetry) from 113±4 to 149±4 mm Hg (Δ36 mm Hg) over the 7-day infusion period, and that effect was blocked in IL-6 KO mice (119±7 to 126±7 mm Hg). RBF decreased to an average of 61±8% of control over the 7-day period (control: 0.86±0.02 mL/min) in the WT mice; however, the average decrease to 72±6% of control (control: 0.88±0.02 mL/min) in the KO mice was not significantly different. There also was no difference in afferent arteriolar constriction by Ang II in blood-perfused juxtamedullary nephrons in WT versus KO mice. Phosphorylation of janus kinase 2 and signal transducer and activator of transcription 3 in renal cortex homogenates increased significantly in Ang II-infused WT mice, and that effect was prevented completely in Ang II-infused IL-6 KO mice. These data suggest that IL-6-dependent activation of the renal janus kinase 2/signal transducer and activator of transcription 3 pathway plays a role in Ang II hypertension but not by mediating the effect of Ang II to decrease total RBF.

Original languageEnglish (US)
Pages (from-to)879-884
Number of pages6
JournalHypertension
Volume56
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • JAK2
  • STAT3
  • angiotensin II
  • blood pressure
  • interleukin 6
  • renal blood flow

ASJC Scopus subject areas

  • Internal Medicine

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