Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model.
Am J Physiol Renal Physiol
; 317(5): F1285-F1292, 2019 11 01.
Article
in En
| MEDLINE
| ID: mdl-31461352
ABSTRACT
Hypoxia is thought to influence the pathogenesis of chronic kidney disease, but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates chronic kidney disease is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n = 54) or sham surgery (sham; n = 52). Twenty-six sham rats and 26 Nx rats remained in normoxia, whereas 26 sham rats and 28 Nx rats were kept in a normobaric hypoxia chamber (12% O2) for 8 wk. Hypoxia was confirmed by immunohistochemistry for pimonidazole. Hypoxia was confined to the medullary area in sham + normoxia rats and spread to the cortical area in sham + hypoxia rats, without changing the peritubular capillary density. Exposure to hypoxia promoted no renal injury or elevation of the content of IL-1ß or Toll-like receptor 4 in sham rats. In Nx, hypoxia also extended to the cortical area without ameliorating the peritubular capillary rarefaction but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury, and oxidative stress. The present study, in disagreement with current concepts, shows evidence that hypoxia exerts a renoprotective effect in the Nx model instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear and may involve NF-κB inhibition, amelioration of oxidative stress, and limitation of angiotensin II production by the renal tissue.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunity, Innate
/
Kidney
/
Hypoxia
/
Nephrectomy
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Renal Physiol
Journal subject:
FISIOLOGIA
/
NEFROLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Brazil