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Augmented endothelial‐specific L ‐arginine transport prevents obesity‐induced hypertension
Author(s) -
Rajapakse N. W.,
Karim F.,
Straznicky N. E.,
Fernandez S.,
Evans R. G.,
Head G. A.,
Kaye D. M.
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.12344
Subject(s) - nitrite , endocrinology , medicine , nitric oxide , endothelial dysfunction , obesity , arginine , nitrate , chemistry , endothelium , amino acid , biochemistry , organic chemistry
Aim Hypertension is a major clinical complication of obesity. Our previous studies show that abnormal uptake of the nitric oxide precursor L ‐arginine, via the cationic amino acid transporter‐1 ( CAT 1), contributes to endothelial dysfunction in cardiovascular disease. In this study, we tested the hypothesis that abnormal L ‐arginine transport may be a key mediator of obesity‐induced hypertension. Methods Mean arterial pressure ( MAP ) was monitored by telemetry in conscious wild‐type ( WT ; n = 13) mice, and transgenic mice with endothelial‐specific overexpression of CAT 1 ( CAT +; n = 14) fed a normal or a high fat diet for 20 weeks. Renal angiotensin II ( A ng II ), CAT 1 m RNA and plasma nitrate/nitrite levels were then quantified. In conjunction, plasma nitrate/nitrite levels were assessed in obese normotensive ( n = 15) and obese hypertensive subjects ( n = 15). Results Both genotypes of mice developed obesity when fed a high fat diet ( P ≤ 0.002). Fat fed WT mice had 13% greater MAP and 78% greater renal A ng II content, 42% lesser renal CAT 1 m RNA levels and 42% lesser plasma nitrate/nitrite levels, than WT mice fed a normal fat diet ( P ≤ 0.02). In contrast, none of these variables were significantly altered by high fat feeding in CAT + mice ( P ≥ 0.36). Plasma nitrate/nitrite levels were 17% less in obese hypertensives compared with obese normotensives ( P = 0.02). Conclusion Collectively, these data indicate that obesity‐induced down‐regulation of CAT 1 expression and subsequent reduced bioavailability of nitric oxide may contribute to the development of obesity‐induced hypertension.