title: Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.
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 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.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salsoso
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Enrique
authors.initials: E
authors.lastname: Guzmán-Gutiérrez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Arroyo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salomón
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Ruiz-Armenta
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio Jesús
authors.initials: AJ
authors.lastname: Blanca
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile ; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, Queensland, Australia.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D027981:Symporters; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C000705567:Slc22a4 protein, rat; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D000070590:Solute Carrier Proteins; D027981:Symporters; D012964:Sodium; D015740:Calcitonin Gene-Related Peptide; D002331:Carnitine