Abstract P247: Tumor Necrosis Factor-alpha Receptors (Type 1 & Type 2) are Differentially Expressed in Renal Tissues During Chronic Dietary Intake of High Salt and Angiotensin II Treatment
Tumor necrosis factor-alpha (TNF-α) exerts natriuresis that is mediated by its’ receptor type 1 (TNFR1) while its’ receptor type 2 (TNFR2) is involved in mediating inflammatory renal injury. To determine the differential roles of these receptors in angiotensin II (AngII) induced salt-sensitive hypertension and associated renal injury, protein expressions of TNFR1 and TNFR2 were examined in mice (n=6-7 in each group) chronically treated with or without AngII (25 ng/min; implanted minipump) for 4 weeks which were fed either normal (NS; 0.4% NaCl) or high salt (HS; 4% NaCl) diets. Systemic blood pressure (SBP) in these mice was measured by tail-cuff plethysmography and 24 hour urine collections were made using metabolic cages at the start and at the end of treatment period when the kidneys were harvested after sacrificing the mice with euthanasia. Immuno-histochemical analysis of TNFR1 and TNFR2 proteins in renal slices was performed by measuring the staining area as well as the intensity of receptors’ immunoreactivities using NIS Elements Software (Nikon), which allowed the semi-quantitation of positive staining and the intensity of these proteins. The results were expressed in percent area of positive staining and the relative intensity. HS intake alone did not alter mean SBP (HS; 77±1 vs NS; 76±3 vs mmHg) but it caused an exaggeration of AngII induced increases in mean SBP (AngII+HS; 104±2 vs AngII+NS; 95±2 mmHg). The area of TNFR1 staining was higher in HS (6.0± 0.9 vs 3.2 ±0.7%; P<0.05) than NS group but it was not significantly different between AngII+HS (5.0± 0.7%) and AngII+NS groups (6.3±0.7%). Similar qualitative differences were also observed in relative intensity in protein expressions. TNFR2 immunoreactivity was minimal in NS and HS groups but it was high in AngII+NS group and even greater in AngII + HS group. These data suggest that the increases in TNFR1 activity due to HS alone facilitate salt excretion that results no change in SBP in response to HS intake. However, such HS induced increases in TNFR1 activity was compromised in elevated AngII condition causing more salt retention and thus, exaggerated hypertensive response. On the other hand, HS induced increases in TNFR2 activity in elevated AngII condition facilitates enhanced renal injury response.
Author Disclosures: D.S.A. Majid: None. M.C. Prieto: None. A. Castillo: None.
- © 2015 by American Heart Association, Inc.