Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules

Xueping Zhou, Pingnian He

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26 Scopus citations


AimsIn this study, we investigated the mechanisms by which caveolin-1 (CAV) inhibits increases in permeability induced by platelet activating factor (PAF) and elucidated the relationship between the endothelial intracellular Ca 2+ concentration ([Ca2+]i) and CAV in regulating endothelial nitric oxide synthase (eNOS) activity and microvessel permeability in intact microvessels.Methods and resultsExperiments were conducted in individually perfused mesenteric venules in Sprague-Dawley rats. Permeability was determined by measuring hydraulic conductivity (Lp). Endothelial [Ca 2+]i and nitric oxide (NO) production were measured in fura-2-and DAF-2-loaded microvessels. Perfusion of the CAV scaffolding domain, AP-CAV, at 1 M for 30 min did not affect PAF-induced increases in endothelial [Ca 2+]i but significantly attenuated PAF-induced NO production from 143 ± 2 to 110 ± 3 of control fluorescence intensity (FI). The PAF-induced Lp increase was correlatively reduced from a mean peak value of 7.5 ± 0.9 to 1.9 ± 0.5 times that of the control. Increasing extracellular [Ca2+] that potentiated PAF-induced peak [Ca 2+]i from 500 to 1225 nM augmented NO production to 193 ± 13 and further increased Lp to 17.3 ± 1.6 times the control value. More importantly, enhanced Ca2+ influx restored the reduced NO production and Lp by AP-CAV with NO FI at 149 and Lp at 7.7 ± 1.1 times the control value.ConclusionOur results indicate that eNOS inhibition and reduced NO production contribute to the inhibitory action of AP-CAV on PAF-induced increases in permeability. CAV and endothelial [Ca2+]i antagonistically regulate eNOS activity in intact microvessels, and the level of produced NO is the key determinant of the degree of permeability increases during inflammation.

Original languageEnglish (US)
Pages (from-to)340-347
Number of pages8
JournalCardiovascular Research
Issue number2
StatePublished - Jul 2010

All Science Journal Classification (ASJC) codes

  • General Medicine


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