Cargando…
Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action
The aim of the present study was to assess quercetin’s mechanism of action in rat pial microvessels during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized using fluorescence microscopy through a closed cranial window. Pial arterio...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338068/ https://www.ncbi.nlm.nih.gov/pubmed/22557973 http://dx.doi.org/10.3389/fphys.2012.00099 |
_version_ | 1782231148202557440 |
---|---|
author | Lapi, D. Vagnani, S. Pignataro, G. Esposito, E. Paterni, M. Colantuoni, A. |
author_facet | Lapi, D. Vagnani, S. Pignataro, G. Esposito, E. Paterni, M. Colantuoni, A. |
author_sort | Lapi, D. |
collection | PubMed |
description | The aim of the present study was to assess quercetin’s mechanism of action in rat pial microvessels during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized using fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction of capillary perfusion. Quercetin highest dose determined dilation in all arteriolar orders, by 40 ± 4% of baseline in order 2 vessels, and prevented microvascular permeability [0.15 ± 0.02 normalized gray levels (NGL)], leukocyte adhesion, and capillary failure. Protein kinase C (PKC) inhibition exerted by chelerythrine prior to quercetin attenuated quercetin-induced effects: order 2 arterioles dilated by 19.0 ± 2.4% baseline, while there was an increase in permeability (0.40 ± 0.05 NGL) and leukocyte adhesion with a marked decrease in capillary perfusion. Tyrosine kinase (TK) inhibition by tyrphostin 47 prior to quercetin lessened smaller pial arterioles responses, dilating by 20.7 ± 2.5% of baseline, while leakage increased (0.39 ± 0.04 NGL) sustained by slight leukocyte adhesion and ameliorated capillary perfusion. Inhibition of endothelium nitric oxide synthase (eNOS) by N(G)-nitro-L-arginine-methyl ester (L-NAME) prior to PKC or TK reduced the quercetin’s effects on pial arteriolar diameter and leakage. eNOS inhibition by L-NAME reduced quercetin effects on pial arteriolar diameter and leakage. Finally, combined inhibition of PKC and TK prior to quercetin abolished quercetin-induced effects, decreasing eNOS expression, while blocking ATP-sensitive potassium (K(ATP)) channels by glibenclamide suppressed arteriolar dilation. In conclusion, the protective effects of quercetin could be due to different mechanisms resulting in NO release throughout PKC and TK intracellular signaling pathway activation. |
format | Online Article Text |
id | pubmed-3338068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33380682012-05-03 Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action Lapi, D. Vagnani, S. Pignataro, G. Esposito, E. Paterni, M. Colantuoni, A. Front Physiol Physiology The aim of the present study was to assess quercetin’s mechanism of action in rat pial microvessels during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized using fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction of capillary perfusion. Quercetin highest dose determined dilation in all arteriolar orders, by 40 ± 4% of baseline in order 2 vessels, and prevented microvascular permeability [0.15 ± 0.02 normalized gray levels (NGL)], leukocyte adhesion, and capillary failure. Protein kinase C (PKC) inhibition exerted by chelerythrine prior to quercetin attenuated quercetin-induced effects: order 2 arterioles dilated by 19.0 ± 2.4% baseline, while there was an increase in permeability (0.40 ± 0.05 NGL) and leukocyte adhesion with a marked decrease in capillary perfusion. Tyrosine kinase (TK) inhibition by tyrphostin 47 prior to quercetin lessened smaller pial arterioles responses, dilating by 20.7 ± 2.5% of baseline, while leakage increased (0.39 ± 0.04 NGL) sustained by slight leukocyte adhesion and ameliorated capillary perfusion. Inhibition of endothelium nitric oxide synthase (eNOS) by N(G)-nitro-L-arginine-methyl ester (L-NAME) prior to PKC or TK reduced the quercetin’s effects on pial arteriolar diameter and leakage. eNOS inhibition by L-NAME reduced quercetin effects on pial arteriolar diameter and leakage. Finally, combined inhibition of PKC and TK prior to quercetin abolished quercetin-induced effects, decreasing eNOS expression, while blocking ATP-sensitive potassium (K(ATP)) channels by glibenclamide suppressed arteriolar dilation. In conclusion, the protective effects of quercetin could be due to different mechanisms resulting in NO release throughout PKC and TK intracellular signaling pathway activation. Frontiers Research Foundation 2012-04-27 /pmc/articles/PMC3338068/ /pubmed/22557973 http://dx.doi.org/10.3389/fphys.2012.00099 Text en Copyright © 2012 Lapi, Vagnani, Pignataro, Esposito, Paterni and Colantuoni. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Physiology Lapi, D. Vagnani, S. Pignataro, G. Esposito, E. Paterni, M. Colantuoni, A. Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title | Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title_full | Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title_fullStr | Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title_full_unstemmed | Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title_short | Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin’s Mechanism of Action |
title_sort | rat pial microvascular responses to transient bilateral common carotid artery occlusion and reperfusion: quercetin’s mechanism of action |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338068/ https://www.ncbi.nlm.nih.gov/pubmed/22557973 http://dx.doi.org/10.3389/fphys.2012.00099 |
work_keys_str_mv | AT lapid ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction AT vagnanis ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction AT pignatarog ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction AT espositoe ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction AT paternim ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction AT colantuonia ratpialmicrovascularresponsestotransientbilateralcommoncarotidarteryocclusionandreperfusionquercetinsmechanismofaction |