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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2010-11, Vol.56 (5), p.879-884
• Main Authors: Brands, Michael W, Banes-Berceli, Amy K.L, Inscho, Edward W, Al-Azawi, Hind, Allen, Ashlyn J, Labazi, Hicham
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Angiotensin II - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - genetics; Blotting, Western; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Dose-Response Relationship, Drug; Hypertension - chemically induced; Hypertension - genetics; Hypertension - metabolism; Immunoenzyme Techniques; Interleukin-6 - genetics; Interleukin-6 - metabolism; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Kidney - blood supply; Kidney - metabolism; Medical sciences; Mice; Mice, Knockout; Phosphorylation - physiology; Random Allocation; Renal Circulation - drug effects; Signal Transduction - drug effects; Signal Transduction - genetics; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Vasoconstriction - drug effects; Vasoconstriction - physiology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.110.158071

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 (control0.86±0.02 mL/min) in the WT mice; however, the average decrease to 72±6% of control (control0.88±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.