AbstractAimHypertension 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.MethodsMean 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 mRNA 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).ResultsBoth 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 mRNA 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).ConclusionCollectively, 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.