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Endothelial cationic amino acid transporter‐1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice
Author(s) -
Konstantinidis G.,
Head G. A.,
Evans R. G.,
NguyenHuu T.P.,
Venardos K.,
Croft K. D.,
Mori T. A.,
Kaye D. M.,
Rajapakse N. W.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12215
Subject(s) - oxidative stress , medicine , endocrinology , superoxide dismutase , mean arterial pressure , blood pressure , endothelium , pathogenesis , endothelial dysfunction , arginine , isoprostane , chemistry , heart rate , pharmacology , amino acid , biochemistry , lipid peroxidation
Aim Oxidative stress may play an important role in the pathogenesis of hypertension. The aim of our study is to examine whether increased expression of the predominant endothelial l ‐arginine transporter, cationic amino acid transporter‐1 ( CAT 1), can prevent oxidative stress‐induced hypertension. Methods Wild‐type mice ( WT ; n = 9) and endothelial CAT 1 overexpressing ( CAT +) mice ( n = 6) had telemetry probes implanted for the measurement of mean arterial pressure ( MAP ), heart rate ( HR ) and locomotor activity. Minipumps were implanted for infusion of the superoxide dismutase inhibitor diethyldithiocarbamic acid ( DETCA ; 30 mg kg −1 day −1 ; 14 days) or its saline vehicle. Baseline levels of MAP , HR and locomotor activity were determined before and during chronic DETCA administration. Mice were then killed, and their plasma and kidneys collected for analysis of F 2 ‐isoprostane levels. Results Basal MAP was less in CAT + (92 ± 2 mmHg; n = 6) than in WT (98 ± 2 mmHg; n = 9; P < 0.001). During DETCA infusion, MAP was increased in WT (by 4.2 ± 0.5%; P < 0.001) but not in CAT +, when compared to appropriate controls ( P DETCA*genotype = 0.006). DETCA infusion increased total plasma F 2 ‐isoprostane levels (by 67 ± 11%; P = 0.05) in WT but not in CAT +. Total renal F 2 ‐isoprostane levels were greater during DETCA infusion in WT (by 72%; P < 0.001), but not in CAT +, compared to appropriate controls. Conclusion Augmented endothelial l ‐arginine transport attenuated the prohypertensive effects of systemic and renal oxidative stress, suggesting that manipulation of endothelial CAT 1 may provide a new therapeutic approach for the treatment of cardiovascular disease associated with oxidative stress.