Abstract: SA-PO1082

Chronic Hypoxia Attenuated Hypertension and Renal Injury in an L-NAME Model

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Rempel, Lisienny CT, Univ of Sao Paulo, Sao Paulo, Brazil
  • Malheiros, Denise M., Univ of Sao Paulo, Sao Paulo, Brazil
  • Camara, Niels OS, 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
  • Albino, Amanda H., Univ of Sao Paulo, Sao Paulo, Brazil
  • Oliveira, Karin C, Univ of Sao Paulo, Sao Paulo, Brazil
  • Zambom, Fernanda FF, Univ of Sao Paulo, Sao Paulo, Brazil
  • Arias, Simone C A, Univ of Sao Paulo, Sao Paulo, Brazil
  • Avila, Victor F, Univ of Sao Paulo, Sao Paulo, Brazil
  • Fanelli, Camilla, Univ of Sao Paulo, Sao Paulo, Brazil
  • Sena, Claudia R., Univ of Sao Paulo, Sao Paulo, Brazil
  • Viana, Vivian L, Univ of Sao Paulo, Sao Paulo, Brazil
Background

Tissue hypoxia has been postulated as a central factor in the pathogenesis of Chronic Kidney Disease (CKD). We showed recently that, rather than worsening renal injury, chronic hypoxia promoted renoprotection in the remannt kidney model. Here we investigated whether chronic hypoxia promotes similar renoprotection in the chronic NO inhibition model

Methods

Male Munich-Wistar rats received Nω-nitroarginine methylester (NAME) in drinking water (80 mg/Kg/day). Sixteen C (Cnor) and 13 NAME rats (NAMEnor) remained in normoxia (21% O2), while 16 C (Chyp) and 16 NAME rats (NAMEhyp) were kept in a normobaric hypoxia chamber (12% O2). After 4 weeks, we assessed: body weight (BW, g), hemoglobin (Hb, g/dL), tail-cuff pressure (TCP, mmHg), urine albumin/creatinine (Ualb/Ucr), glomerulosclerosis (GS, %), ischemic glomeruli (IG, %), cortical interstitium (INT, %), interstitial macrophages (MΦ, cells/mm2) and Angiotensin II positive cell (AngII, cells/mm2) as well as nuclear p65 content (NF-kB, x Cnor). Renal hypoxia was confirmed by pimonidazole immunohistochemistry.

Results

Hypoxia was confined to the outer medulla in Cnor and spread to the cortical area in Chyp. In NAMEnor, hypoxia also extended to the cortical area, a process that was intensified in NAMEhyp. In agreement with our findings in the remnant kidney model, hypoxia attenuated hypertension, inflammation and renal injury, in association with decreased infiltration by Ang II+ cells.

Conclusion

As in the remnant kidny model, chronic hypoxia limited inflammation as well as glomerular and interstitial injury in the chronic NO inhibition model, suggesting that this may be a universal effect. FAPESP/CNPq

 BWHbTCPUalb/UCrGSIGINTAngIINF-κB
Cnor286±414±1141±30.1±0.10.1±0.10.5±0.30.1±0.130±41.6±0.41.0±0.3
NAMEnor249±8a14±1202±5a4.3±0.8a1.1±0.3a6.9±0.9a1.3±0.3a114±14a4.6±0.8a2.4±0.5a
Chyp268±4b16±1b137±30.3±0.10.1±0.30.4±0.30.1±0.132±31.7±0.61.0±0.2
NAMEhyp251±517±1b161±3ab0.6±0.2b0.1±0.1b0.4±0.1b0.1±0.1b46±6b1.7±0.4b1.3±0.2

Funding

  • Government Support - Non-U.S.