Abstract 514: Caspase-1 Activation Contributes to Angiotensin-II-induced Vascular Dysfunction and Hypertension
Caspase-1 (casp-1) regulates key steps in microbial and sterile inflammatory responses. Hypertension is associated with inflammation of the vascular wall, but it is not known whether casp-1 mediates this phenomenon. We hypothesized that casp-1 contributes to vascular dysfunction in angiotensin II (AngII)-induced hypertension.
Male C57BL/6 wild type (WT) and casp-1 knockout (casp-1-/-) mice were infused with AngII (90 ng/min, 14 days, osmotic mini-pumps). Control mice were sham-operated. Systolic blood pressure (SBP, mmHg) was significantly increased in AngII-WT mice (162±7.9 vs.138±2.9 WT-sham, p<0.05), however this elevation was less in AngII-casp-1-/- mice (148±13 vs. 140±6.2 casp-1-/--sham, p>0.05). AngII-WT mice exhibited cardiac hypertrophy (mg/g: 10±0.36 vs. 4.9±0.19 WT-sham, p<0.05), which was not observed in AngII-casp-1-/- mice (mg/g: 7.6±0.70 vs. 5.6±0.68 casp-1-/--sham, p>0.05). Severe endothelial dysfunction [acetylcholine (ACh)-dependent dilation, second-order mesenteric arteries] was observed in AngII-WT mice, but this was attenuated in AngII-casp-1-/- mice (inserted Figure). Vascular superoxide anion production (dihydroethidium fluorescence, arbitrary units) augmented in AngII-WT (6.2±0.60 vs. 4.9±0.48 WT-sham, p<0.05), but not in AngII-casp-1-/- (4.9±0.48 vs. 4.0±0.64 casp-1-/--sham, p>0.05) mice. Preliminary data also show that AngII in vivo and in vitro induces casp-1 activation (western blotting for cleaved casp-1). These data provide evidence that activation of casp-1 plays a role in vascular dysfunction associated with AngII-hypertension.
- © 2012 by American Heart Association, Inc.