SUN-211 TISSUE HYPOXIA ATTENUATED RATHER THAN AGGRAVATED RENAL INJURY AND INFLAMMATION IN RATS WITH CHRONIC NO INHIBITION

Abstract

Chronic NO inhibition by Nω-nitroarginine methylester (NAME) leads to severe hypertension (HT) and renal parenchymal/vascular injury. Tissue hypoxia has been postulated as a pathogenic factor of Chronic Kidney Disease (CKD), but we showed recently that chronic hypoxia promoted renoprotection in the remnant kidney model. In the present study, we sought to determine whether similar renoprotection would be observed in NAME rats maintained under hypoxia. Adult male Munich Wistar rats were given NAME, 80 mg/kg/day in drinking water. Sixteen C (CNOR) and 13 NAME (NAMENOR) rats remained in normoxia (NOR, 21% O2), while 16 C (CHYP) and 16 NAME (NAMEHYP) rats remained under normobaric hypoxia (HYP, 12% O2). After 4 wk, body weight (BW, g), hemoglobin (Hb, g/dL), hematocrit (Ht, %) tail-cuff pressure (TCP, mmHg), urine albumin/creatinine (Ualb/Ucr), glomerulosclerosis (GS, %), ischemic glomeruli (IG,%), interstitial macrophages, and angiotensin II+ cells (MΦ and AngII+, cells/mm2), and the renal content of nuclear NF-kB and IL1β (pg/mg) were assessed. Renal hypoxia was confirmed by pimonidazole immunohistochemistry. Tabled 1CNORNAMENORCHYPNAMEHYPBW306±11285±8294±5277±6Hb14±115±117±117±1#Ht52±153±163±165±1#TCP151±2212±2*154±4188±6*#UALB/UCREAT0.2±0.11.8±0.4*0.3±0.10.7±0.1#Screat0.6±0.10.7±0.10.7±0.10.7±0.1GS%0.1±0.11.1±0.3*0.1±0.30.1±0.1#GI%0.5±0.36.9±0.9*0.4±0.30.4±0.1#MfINT30±4114±14*32±346±6#Ang II1.6±0.44.6±0.8*1.7±0.61.7±0.4#NF-κB1.0±0.32.4±0.5*1.0±0.21.3±0.2#IL-1β2.6±0.66.4±0.9*3.8±0.72.9±0.3#(Mean±SE)∗p<0.05 vs respective C#p<0.05 vs NAMENOR) Open table in a new tab (Mean±SE) ∗p<0.05 vs respective C #p<0.05 vs NAMENOR) Hypoxia, assessed by pimonidazole staining, was restricted to the outer medullary region in CNOR, but extended to the cortical area in CHYP. In NAMENOR, hypoxia also reached the cortical area, a process that was intensified in NAMEHYP. In consistency with our previous observation in remnant kidneys, hypoxia attenuated hypertension and renal injury/inflammation, along with diminished renal NF-kB and IL-1β content. In consistency with our findings in remnant kidneys, hypoxia attenuated renal innate immunity activation and inflammation, as well as glomerular and interstitial injury in the chronic NO inhibition model, indicating that this protective effect is not restricted to a single CKD model. FAPESP/CNPq.