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Am J Physiol Renal Physiol
2014[Jun]; 306
(12
): F1499-506
PMID24761000
show ga
Oxidative stress promotes vascular dysfunction in chronic kidney disease (CKD).
We utilized the cutaneous circulation to test the hypothesis that reactive oxygen
species derived from NADPH oxidase and xanthine oxidase impair nitric oxide
(NO)-dependent cutaneous vasodilation in CKD. Twenty subjects, 10 stage 3 and 4
patients with CKD (61 ± 4 yr; 5 men/5 women; eGFR: 39 ± 4 ml·min(-1)·1.73 m(-2))
and 10 healthy controls (55 ± 2 yr; 4 men/6 women; eGFR: >60 ml·min(-1)·1.73
m(-2)) were instrumented with 4 intradermal microdialysis fibers for the delivery
of 1) Ringer solution (Control), 2) 10 ?M tempol (scavenge superoxide), 3) 100 ?M
apocynin (NAD(P)H oxidase inhibition), and 4) 10 ?M allopurinol (xanthine oxidase
inhibition). Skin blood flow was measured via laser-Doppler flowmetry during
standardized local heating (42°C). N(g)-nitro-l-arginine methyl ester (L-NAME; 10
mM) was infused to quantify the NO-dependent portion of the response. Cutaneous
vascular conductance (CVC) was calculated as a percentage of the maximum CVC
achieved during sodium nitroprusside infusion at 43°C. Cutaneous vasodilation was
attenuated in patients with CKD (77 ± 3 vs. 88 ± 3%, P = 0.01), but augmented
with tempol and apocynin (tempol: 88 ± 2 (P = 0.03), apocynin: 91 ± 2% (P =
0.001). The NO-dependent portion of the response was reduced in patients with CKD
(41 ± 4 vs. 58 ± 2%, P = 0.04), but improved with tempol and apocynin (tempol: 58
± 3 (P = 0.03), apocynin: 58 ± 4% (P = 0.03). Inhibition of xanthine oxidase did
not alter cutaneous vasodilation in either group (P > 0.05). These data suggest
that NAD(P)H oxidase is a source of reactive oxygen species and contributes to
microvascular dysfunction in patients with CKD.
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