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

Xueping Zhou, Pingnian He

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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
Volume87
Issue number2
DOIs
StatePublished - Jul 1 2010

Fingerprint

Caveolin 1
Venules
Nitric Oxide Synthase Type III
Microvessels
Platelet Activating Factor
Permeability
Nitric Oxide
Transcription Factor AP-1
Fluorescence
Fura-2
Sprague Dawley Rats
Perfusion
Inflammation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{a5f2c99037954b20a1f08a41e1fb1cff,
title = "Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules",
abstract = "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.",
author = "Xueping Zhou and Pingnian He",
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Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules. / Zhou, Xueping; He, Pingnian.

In: Cardiovascular Research, Vol. 87, No. 2, 01.07.2010, p. 340-347.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules

AU - Zhou, Xueping

AU - He, Pingnian

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N2 - 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.

AB - 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.

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