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ATP mediates flow‐induced nitric oxide production in thick ascending limbs
Author(s) -
Cabral Pablo Daniel,
Garvin Jeffrey Lawrence
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.812.18
Subject(s) - apyrase , chemistry , nitric oxide , suramin , extracellular , biophysics , stimulation , receptor , biochemistry , endocrinology , biology , organic chemistry
Mechanical stimulation caused by increasing flow induces the release of ATP and other nucleotides. Both luminal flow and extracellular ATP stimulate production of nitric oxide (NO) in the thick ascending limb (TAL). We hypothesized that luminal flow‐induced NO production in TALs is mediated by ATP. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. The rate of increase in fluorescence reflects NO accumulation. Increasing luminal flow from 0 to 20 nL/min stimulated NO production from 17±15 to 130±34 arbitrary units (AU)/min (p < 0.04; n=7). When an ATP scavenging system (hexokinase; 10 U/ml plus 5.5 mM glucose) was added to the luminal perfusate and basolateral bath, luminal flow did not increase NO production (control: 32±5; after ATP scavenging: 19±4 AU/min; n=6). When luminal flow was increased with the ATPase apyrase (5 U/ml) in the luminal perfusate and basolateral bath, NO levels did not change significantly (control: 41±12; after apyrase: 59±11; n=6). The P2 receptor antagonist suramin (300 umol/L) in the lumen and bath reduced flow‐induced NO production by 73% (control: 56±11; with suramin: 13±12; n=5). We concluded that ATP mediates flow‐induced NO production in thick ascending limbs via P2 receptors. Support: PO1 HL 090550, RO1 HL 070985