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Increased nitric oxide is necessary but not sufficient to increase permeability in the absence of calcium influx in intact rat venules
Author(s) -
Wang Mingxia,
Yuan Dong,
He Pingnian
Publication year - 2012
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.26.1_supplement.855.2
Subject(s) - chemistry , nitric oxide , permeability (electromagnetism) , microvessel , endocrinology , calcium , medicine , biophysics , enos , nitric oxide synthase , biochemistry , biology , immunohistochemistry , organic chemistry , membrane
Our studies showed that inhibition of nitric oxide synthase (NOS) prevented inflammatory stimuli‐induced permeability increases without affecting the initial increase in endothelial (EC) [Ca 2+ ] i , suggesting that eNOS activation downstream from Ca 2+ signal is the key determinant of permeability increases. However, we also found that H 2 O 2 ‐induced initial NO production does not cause an immediate permeability increase in the absence of an initially increased EC [Ca 2+ ] i . We therefore hypothesize that increased NO alone is not sufficient to increase permeability in the absence of increased EC [Ca 2+ ] i . To test this hypothesis, microvessel permeability was measured by hydraulic conductivity Lp in individually perfused rat venules. Increased NO was initiated by NO donors and confirmed by DAF‐2 measurements. Increased EC [Ca 2+ ] i was induced by platelet activating factor (PAF, 10 nM). Results showed that perfusing Spermine NONOate (100 μM) or S‐Nitroso‐ N‐acetyl‐D, L‐penicillamine (SNAP, 400 μM) alone did not increase Lp, but both NO donors potentiated PAF‐induced Lp peak from 9 ± 1.2 (without NO donor) to 43 ± 13.0 and 27 ± 4.1 times the control value. These results support the hypothesis that increasing NO alone is not sufficient to increase permeability in the absence of Ca 2+ influx, but in the presence of stimuli‐induced Ca 2+ signal, the higher NO level potentiated the increased permeability. The results suggest that increased NO and EC [Ca 2+ ] i are both necessary and function co‐dependently to increase microvessel permeability. Supported by HL56237 and HL084338.