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Kidney Week

Abstract: FR-PO358

Hypoxia Reduced Renal Injury and Inflammation in Rats with Chronic Nitric Oxide Inhibition

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Zambom, Fernanda FF, Univ of Sao Paulo, Sao Paulo, Brazil
  • Albino, Amanda H., Univ of Sao Paulo, Sao Paulo, Brazil
  • Tessaro, Helena Mendonca, Univ of Sao Paulo, Sao Paulo, Brazil
  • Foresto-Neto, Orestes, Univ of Sao Paulo, Sao Paulo, Brazil
  • Rempel, Lisienny CT, Univ of Sao Paulo, Sao Paulo, Brazil
  • Pião, Janice, Univ of Sao Paulo, Sao Paulo, Brazil
  • Malheiros, Denise M., Univ of Sao Paulo, Sao Paulo, Brazil
  • Camara, Niels Olsen Saraiva, Univ of Sao Paulo, Sao Paulo, Brazil
  • Fujihara, Clarice K., Univ of Sao Paulo, Sao Paulo, Brazil
  • Zatz, Roberto, Univ of Sao Paulo, Sao Paulo, Brazil
Background

Chronic NO inhibition by Nω-nitroarginine methylester (NAME) leads to severe hypertension (HT) and Chronic Kidney Disease (CKD). Tissue hypoxia (HYP) has been postulated as a pathogenic factor in CKD, but we showed recent evidence that it may instead be renoprotective. We investigated whether this salutary effect would also be observed in NAME rats and whether it would involve NLRP3 and/or NFκB inhibition.

Methods

Male Munich-Wistar rats received NAME, 80 mg/kg/d in tap water. Ten Control (C) and 10 NAME rats were kept under 21% O2 (NOR), while 12 C and 12 NAME rats breathed 12% O2. After 4 wk, we assessed hemoglobin (Hb,g/dL), tail-cuff pressure (TCP, mmHg), urine albumin/creatinine (UAlb/UCr), glomerulosclerosis (GS, %), % ischemic glomeruli (% IG), cortical density (mm-2) of macrophages (MΦ), Angiotensin II+ (AII+) and NLRP3+ cells, cortical Collagen-1 (%Coll-1) and the renal content of nuclear p65, IL6, Casp1, HO1 and SOD2 (WB), and IL1β (pg/mg). HYP was confirmed by pimonidazole staining.

Results

HYP reduced HT, inflammation, oxidative stress, renal injury, and the content of NLRP3, CASP1, IL1β, nuclear p65 and IL6.

Conclusion

Tissue HYP exerted a protective effect in NAME, suggesting that it may influence a common pathogenic mechanism, which may relate to downregulation of the NLRP3 inflammasome/Casp1/IL1β and NFκB/IL6 pathways, and to limitation of oxidative stress. FAPESP/CNPq.

 CNORNAMENORCHYPNAMEHYP
Hb14±115±117±1*17±1#
TCP151±2212±2*154±4188±6*#
UAlb/UCr0.2±0.11.8±0.4*0.3±0.10.7±0.1#
%GS0.1±0.11.1±0.3*0.1±0.30.1±0.1#
%IG0.5±0.36.9±0.9*0.4±0.30.4±0.1#
30±4114±14*32±346±6*#
AII+2±15±1*2±12±1#
%Coll12.4±0.26.1±0.3*3.2±0.23.7±0.2#
Nuclear p651.1±0.23.2±0.5*1.1±0.22.0±0.3#
IL61±0.16.1±1.7*1.6±0.42.5±1.0#
NLRP31±14±1*1±12±1*#
CASP11±0.25.6±2.0*1.7±0.42.2±1.1#
IL1β2.6±0.66.4±0.9*3.8±0.72.9±0.3#
HO11±0.22.3±0.3*1±0.21.9±0.2*
SOD21±0.10.5±0.1*1±0.20.7±0.1

Mean±SE;*p<0.05 vs respect C, #p<0,05 vs NNOR

Funding

  • Government Support - Non-U.S.