title: Augmented endothelial-specific L-arginine transport prevents obesity-induced hypertension.
abstract: OBJECTIVE
  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 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).
  
  
  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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia.
authors.forename: N W
authors.initials: NW
authors.lastname: Rajapakse
authors.forename: F
authors.initials: F
authors.lastname: Karim
authors.forename: N E
authors.initials: NE
authors.lastname: Straznicky
authors.forename: S
authors.initials: S
authors.lastname: Fernandez
authors.forename: R G
authors.initials: RG
authors.lastname: Evans
authors.forename: G A
authors.initials: GA
authors.lastname: Head
authors.forename: D M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000368:Aged; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D009569:Nitric Oxide; D001120:Arginine
keywords: L-arginine transport; hypertension; kidney; nitric oxide; obesity