Interleukin 6 Knockout Prevents Angiotensin II Hypertension Role of Renal Vasoconstriction and Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Activation

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 mmHg (Delta 36 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. (Hypertension. 2010;56:879-884.)