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- Title
Augmented endothelial-specific L-arginine transport prevents obesity-induced hypertension.
- Authors
Rajapakse, N. W.; Karim, F.; Straznicky, N. E.; Fernandez, S.; Evans, R. G.; Head, G. A.; Kaye, D. M.
- Abstract
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 ( CAT1), 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 CAT1 ( CAT+; n = 14) fed a normal or a high fat diet for 20 weeks. Renal angiotensin II ( Ang II), CAT1 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 Ang II content, 42% lesser renal CAT1 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 CAT1 expression and subsequent reduced bioavailability of nitric oxide may contribute to the development of obesity-induced hypertension.
- Subjects
HYPERTENSION; OBESITY; PHYSIOLOGICAL effects of arginine; ENDOTHELIUM; AMINO acid transport
- Publication
Acta Physiologica, 2014, Vol 212, Issue 1, p39
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.12344