Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways.
Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell culture...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00529/full |
| _version_ | 1818293060466900992 |
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| author | Lissette Cabrera Lissette Cabrera Andrea Saavedra Susana Rojas Marcela Cid Cristina Valenzuela David Alejandro Gallegos Rozas Pamela Careaga Emerita Basualto Astrid Haensgen Eduardo Peña Coralia Rivas Juan Carlos Vera Victoria Gallardo Leandro Zuniga Carlos Alonso Escudero Carlos Alonso Escudero Luis Sobrevia Luis Sobrevia Luis Sobrevia Mark Wareing Marcelo González Marcelo González |
| author_facet | Lissette Cabrera Lissette Cabrera Andrea Saavedra Susana Rojas Marcela Cid Cristina Valenzuela David Alejandro Gallegos Rozas Pamela Careaga Emerita Basualto Astrid Haensgen Eduardo Peña Coralia Rivas Juan Carlos Vera Victoria Gallardo Leandro Zuniga Carlos Alonso Escudero Carlos Alonso Escudero Luis Sobrevia Luis Sobrevia Luis Sobrevia Mark Wareing Marcelo González Marcelo González |
| author_sort | Lissette Cabrera |
| collection | DOAJ |
| description | Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analogue) or hydrogen peroxide (H2O2) were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels), iberiotoxin (BKCa channels), genistein (tyrosine kinases) and wortmannin (phosphatidylinositol 3-kinase). Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO. |
| first_indexed | 2024-12-13T03:09:51Z |
| format | Article |
| id | doaj.art-6efc98fd8da8471f9bd5bbf6096717f5 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-13T03:09:51Z |
| publishDate | 2016-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-6efc98fd8da8471f9bd5bbf6096717f52022-12-22T00:01:38ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-11-01710.3389/fphys.2016.00529202821Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways.Lissette Cabrera0Lissette Cabrera1Andrea Saavedra2Susana Rojas3Marcela Cid4Cristina Valenzuela5David Alejandro Gallegos Rozas6Pamela Careaga7Emerita Basualto8Astrid Haensgen9Eduardo Peña10Coralia Rivas11Juan Carlos Vera12Victoria Gallardo13Leandro Zuniga14Carlos Alonso Escudero15Carlos Alonso Escudero16Luis Sobrevia17Luis Sobrevia18Luis Sobrevia19Mark Wareing20Marcelo González21Marcelo González22Universidad de ConcepciónUniversidad Diego PortalesUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de ConcepciónUniversidad de TalcaGroup of Research and Innovation in Vascular Health (Grivas Health)Universidad del BiobíoPontificia Universidad Católica de ChileUniversidad de SevillaUniversity of Queensland Centre for Clinical Research (UQCCR)University of ManchesterUniversidad de ConcepciónGroup of Research and Innovation in Vascular Health (Grivas Health)Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analogue) or hydrogen peroxide (H2O2) were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels), iberiotoxin (BKCa channels), genistein (tyrosine kinases) and wortmannin (phosphatidylinositol 3-kinase). Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00529/fullInsulinNitric OxidePlacentaL-arginineBKCa channels |
| spellingShingle | Lissette Cabrera Lissette Cabrera Andrea Saavedra Susana Rojas Marcela Cid Cristina Valenzuela David Alejandro Gallegos Rozas Pamela Careaga Emerita Basualto Astrid Haensgen Eduardo Peña Coralia Rivas Juan Carlos Vera Victoria Gallardo Leandro Zuniga Carlos Alonso Escudero Carlos Alonso Escudero Luis Sobrevia Luis Sobrevia Luis Sobrevia Mark Wareing Marcelo González Marcelo González Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. Frontiers in Physiology Insulin Nitric Oxide Placenta L-arginine BKCa channels |
| title | Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. |
| title_full | Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. |
| title_fullStr | Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. |
| title_full_unstemmed | Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. |
| title_short | Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways. |
| title_sort | insulin induces relaxation and decreases hydrogen peroxide induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium activated potassium channels and l arginine nitric oxide pathways |
| topic | Insulin Nitric Oxide Placenta L-arginine BKCa channels |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00529/full |
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