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Tumor necrosis factor-? produced in the kidney contributes to angiotensin
II-dependent hypertension
#MMPMID25185128
Zhang J
; Patel MB
; Griffiths R
; Mao A
; Song YS
; Karlovich NS
; Sparks MA
; Jin H
; Wu M
; Lin EE
; Crowley SD
Hypertension
2014[Dec]; 64
(6
): 1275-81
PMID25185128
show ga
Immune system activation contributes to the pathogenesis of hypertension and the
resulting progression of chronic kidney disease. In this regard, we recently
identified a role for proinflammatory Th1 T-lymphocyte responses in hypertensive
kidney injury. Because Th1 cells generate interferon-? and tumor necrosis
factor-? (TNF-?), we hypothesized that interferon-? and TNF-? propagate renal
damage during hypertension induced by activation of the renin-angiotensin system.
Therefore, after confirming that mice genetically deficient of Th1 immunity were
protected from kidney glomerular injury despite a preserved hypertensive
response, we subjected mice lacking interferon-? or TNF-? to our model of
hypertensive chronic kidney disease. Interferon deficiency had no impact on blood
pressure elevation or urinary albumin excretion during chronic angiotensin II
infusion. By contrast, TNF-deficient (knockout) mice had blunted hypertensive
responses and reduced end-organ damage in our model. As angiotensin II-infused
TNF knockout mice had exaggerated endothelial nitric oxide synthase expression in
the kidney and enhanced nitric oxide bioavailability, we examined the actions of
TNF-? generated from renal parenchymal cells in hypertension by transplanting
wild-type or TNF knockout kidneys into wild-type recipients before the induction
of hypertension. Transplant recipients lacking TNF solely in the kidney had
blunted hypertensive responses to angiotensin II and augmented renal endothelial
nitric oxide synthase expression, confirming a role for kidney-derived TNF-? to
promote angiotensin II-induced blood pressure elevation by limiting renal nitric
oxide generation.
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