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Endothelial [Ca2+]i and caveolin‐1 play antagonistic roles in the regulation of NO production and microvessel permeability
Author(s) -
Zhou Xueping,
He Pingnian
Publication year - 2007
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.21.5.a489-a
Subject(s) - microvessel , enos , extracellular , caveolin 1 , chemistry , permeability (electromagnetism) , vascular permeability , biophysics , endothelial stem cell , medicine , endocrinology , in vitro , angiogenesis , biology , biochemistry , membrane , enzyme , nitric oxide synthase
Our previous study demonstrated that platelet activating factor (PAF)‐induced increases in microvessel permeability were accompanied with increases in endothelial cell (EC) [Ca 2+ ]i and NO production, and that exogenously supplied caveolin‐1 scaffolding domain (CAV) attenuated PAF‐induced permeability increase through inhibition of eNOS. This study is to test the hypothesis that EC [Ca 2+ ]i and CAV are competitive and opposing regulators of eNOS and the balance between EC [Ca 2+ ]i and CAV determines NO production and microvessel permeability. Experiments were conducted in individually perfused venular microvessels in rat mesenteries. Permeability was accessed by measuring hydraulic conductivity (Lp) and EC [Ca 2+ ]i was measured in Fura‐2 loaded microvessels. Perfusion of CAV at 1μM or 10μM for 30 min attenuated PAF‐induced Lp increase from a mean peak value of 5.3±1.0 to 1.9±0.5 and 1.8±0.6 times of the control. Increasing extracellular [Ca 2+ ] from 2 to 10 mM potentiated PAF‐induced increase in EC [Ca 2+ ]i from 460±51 to 1243±157 nM and overrode the inhibitory effect of CAV on Lp resulting in 8.5±1.5 fold Lp increase. Our results indicated that exogenously supplied CAV at 1 or 10 μM are sufficient to compete with PAF‐induced [Ca 2+ ]i increase under normal extracellular [Ca 2+ ] and dominates its inhibitory effect on eNOS. Further increased EC [Ca 2+ ]i enables to override the inhibitory effect of CAV on eNOS and resumes the NO production and the increases in Lp. We conclude that the overall balance between EC [Ca 2+ ]i and CAV determines eNOS activity and the increased NO is crucial for increases in microvessel permeability. Supported by AHA GIA and NIH HL56237