Article
Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats
Author/s | Salsoso Rodríguez, Rocío
Guzmán Gutiérrez, Enrique Arroyo Zúñiga, Pablo Salomón Gallo, Carlos Zambrano Sevilla, Sonia Ruiz Armenta, María Victoria Blanca Lobato, Antonio Jesús Pardo, Fabián Leiva Mendoza, Andrea Mate Barrero, Alfonso Sobrevia Luarte, Luis Vázquez Cueto, Carmen María |
Department | Universidad de Sevilla. Departamento de Fisiología |
Publication Date | 2014 |
Deposit Date | 2015-09-23 |
Published in |
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Abstract | 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 ... 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 (Vmax), without changes in apparent Km 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. |
Citation | Salsoso Rodríguez, R., Guzmán Gutiérrez, E., Arroyo Zúñiga, P., Salomón Gallo, C., Zambrano Sevilla, S., Ruiz Armenta, M.V.,...,Vázquez Cueto, C.M. (2014). Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. Plos One, 9 (2), e90339-1-e90339-11. |
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