Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.
Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Ca...
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doaj-fa7ce7a4618f4f05b106531da0e7560e2020-11-24T21:54:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e9033910.1371/journal.pone.0090339Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.Rocío SalsosoEnrique Guzmán-GutiérrezPablo ArroyoCarlos SalomónSonia ZambranoMaría Victoria Ruiz-ArmentaAntonio Jesús BlancaFabián PardoAndrea LeivaAlfonso MateLuis SobreviaCarmen María VázquezImpaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)-independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5-8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1-100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na(+)-dependent (Na(+) dep ) compared with Na(+)-independent (Na(+) indep ) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na(+) indep transport in SHR compared with WKY rats. Total and Na(+) dep component of transport were increased, but Na(+) indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na(+) indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na(+)-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR.http://europepmc.org/articles/PMC3938671?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rocío Salsoso Enrique Guzmán-Gutiérrez Pablo Arroyo Carlos Salomón Sonia Zambrano María Victoria Ruiz-Armenta Antonio Jesús Blanca Fabián Pardo Andrea Leiva Alfonso Mate Luis Sobrevia Carmen María Vázquez |
spellingShingle |
Rocío Salsoso Enrique Guzmán-Gutiérrez Pablo Arroyo Carlos Salomón Sonia Zambrano María Victoria Ruiz-Armenta Antonio Jesús Blanca Fabián Pardo Andrea Leiva Alfonso Mate Luis Sobrevia Carmen María Vázquez Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. PLoS ONE |
author_facet |
Rocío Salsoso Enrique Guzmán-Gutiérrez Pablo Arroyo Carlos Salomón Sonia Zambrano María Victoria Ruiz-Armenta Antonio Jesús Blanca Fabián Pardo Andrea Leiva Alfonso Mate Luis Sobrevia Carmen María Vázquez |
author_sort |
Rocío Salsoso |
title |
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
title_short |
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
title_full |
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
title_fullStr |
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
title_full_unstemmed |
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
title_sort |
reduced l-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)-independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5-8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1-100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na(+)-dependent (Na(+) dep ) compared with Na(+)-independent (Na(+) indep ) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na(+) indep transport in SHR compared with WKY rats. Total and Na(+) dep component of transport were increased, but Na(+) indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na(+) indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na(+)-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR. |
url |
http://europepmc.org/articles/PMC3938671?pdf=render |
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