Abstract 16608: Interleukin-1 Receptor Antagonist Deficiency Promotes Angiotensin II-Induced hypertension and Renal Damage
Background: Angiotensin II (AngII), the main effecter of the rennin-angiotensin system, increases arterial pressure, and activates components of the inflammatory cascade. The interleukin-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a critical role in acute and chronic inflammation. However, the role of IL-1Ra in Ang II-induced hypertension and organ damage remains unknown.
Methods and results: To determine the contribution of IL-1Ra to hypertension, mice were assigned to 4 groups: Ang II infusion at 3000ng/kg per minute in IL-1Ra-deficient (KO)(IL-1Ra KO (AngII))(n=9) and wild-type(WT) (WT (AngII)) (n=8) mice and saline infusion in IL-1Ra KO (IL-1Ra KO (Cont))(n=7) and WT (WT(Cont)) (n=7) mice for 14 days. 14 days after infusion, we observed no significant differences in body weight (WT (Cont): 21.7±0.6, IL-1Ra KO (Cont): 22.3±0.7, WT (AngII):20.7±0.9, IL-1Ra KO (AngII):17.1±0.6g), or pulse rates (737±22, 714±10, 715±14, 633±12/min). However, systolic blood pressure in IL-1Ra KO (AngII) mice significantly increased compared with WT (AngII) mice (172±7 vs. 128±8 mmHg)(P=0.001) (Figure A). Furthermore, we also detected that plasma IL-6 concentration in IL-1Ra KO (AngII) mice (n=4) was 8.9 times higher than WT (AngII) mice (n=7) at 14 days (P<0.01) (Figure B). The renal histological changes (such as decreased Bowman space, decreased capillary lumen, mesangial hypercellularity, and fibrosis in both glomeruli and interstitial areas between tubules) were detected more frequently in IL-1Ra KO (AngII) mice compared with WT (AngII) mice at 14 days post infusion.
Conclusion: The present study shows that IL-1Ra gene deficiency in mice led to the increase of serum IL-6 concentration and the development of hypertension after AngII infusion. Furthermore, our results also showed IL-1Ra protected AngII-induced renal damages.
- © 2013 by American Heart Association, Inc.