title: TNF-α type 2 receptor mediates renal inflammatory response to chronic angiotensin II administration with high salt intake in mice.
abstract: Tumor necrosis factor-alpha (TNF-α) has been implicated in salt-sensitive hypertension and renal injury (RI) induced by angiotensin II (ANG II). To determine the receptor type of TNF-α involved in this mechanism, we evaluated the responses to chronic ANG II infusion (25 ng/min by implanted minipump) given with high-salt diet (HS; 4% NaCl) for 2 wk in gene knockout mice for TNF-α receptor type 1 (TNFR1KO; n = 6) and type 2 (TNFR2KO; n = 6) and compared the responses with those in wild-type (WT; C57BL/6; n = 6) mice. Blood pressure in these mice was measured by implanted radiotelemetry as well as by tail-cuff plethysmography. RI responses were assessed by measuring macrophage cell infiltration (CD68(+) immunohistochemistry), glomerulosclerosis (PAS staining), and interstitial fibrosis (Gomori's trichrome staining) in renal tissues at the end of the treatment period. The increase in mean arterial pressure induced by ANG II + HS treatment was not different in these three groups of mice (TNFR1KO, 114 ± 1 to 161 ± 7 mmHg; TNFR2KO, 113 ± 1 to 161 ± 3 mmHg; WT, 110 ± 3 to 154 ± 3 mmHg). ANG II + HS-induced RI changes were similar in TNFR1KO mice but significantly less in TNFR2KO mice (macrophage infiltration, 0.02 ± 0.01 vs. 1.65 ± 0.45 cells/mm(2); glomerulosclerosis, 26.3 ± 2.6 vs. 35.7 ± 2.2% area; and interstitial fibrosis, 5.2 ± 0.6 vs. 8.1 ± 1.1% area) compared with the RI changes in WT mice. The results suggest that a direct activation of TNF-α receptors may not be required in inducing hypertensive response to chronic ANG II administration with HS intake, but the induction of inflammatory responses leading to renal injury are mainly mediated by TNF-α receptor type 2.
authors: Department of Physiology, Hypertension & Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Purnima
authors: P
authors: Singh
authors: Laleh
authors: L
authors: Bahrami
authors: Alexander
authors: A
authors: Castillo
authors: Dewan S A
authors: DS
authors: Majid
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005921:Glomerulonephritis / Q000139:chemically induced*; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D014554:Urination / Q000187:drug effects / Q000502:physiology
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II
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