Enhanced NO inactivation and hypertension induced by a high-fat, refined-carbohydrate diet.
We have recently demonstrated that long-term consumption of a high-fat, refined-carbohydrate (HFS) diet induces hypertension (HTN) in normal rats compared with a low-fat, complex-carbohydrate (LFCC) diet. Limited evidence suggests that high-fat or high-sugar diets cause enhanced generation of reactive oxygen species (ROS). We therefore hypothesized that by inducing oxidative stress, the HFS diet may promote nitric oxide (NO) inactivation and HTN. To test this hypothesis, female Fischer rats were placed on either the HFS or the LFCC diet starting at 2 months of age. Blood pressure, urinary NO metabolites (NO(x)), and total renal NO synthase activity were monitored, and the tissue abundance of nitrotyrosine (NT), which is the stable "footprint" of NO oxidation by ROS, was determined. The HFS diet group exhibited a gradual rise in arterial blood pressure and were hypertensive by 18 months. This trend was accompanied by a marked accumulation of NT in all tested tissues, an initial rise and a subsequent fall in NO synthase activity, and a fall in urinary NO(x) excretion. The HFS diet-fed animals had a blunted blood pressure response to the NO synthase inhibitor N:(omega)-nitro-L-arginine methyl ester (L-NAME) compared with the LFCC diet group, which showed a marked hypertensive response to L-NAME. L-NAME-induced HTN was reversible with L-arginine in the LFCC diet group; however, HTN was not corrected by L-arginine supplementation in the HFS diet group. These findings point to enhanced ROS-mediated inactivation and sequestration of NO, which may contribute to the reduction of bioactive NO and HTN in the HFS diet-fed animals.
Roberts
C K
CK
Department of Physiological Science, University of California, Los Angeles 90095-1527, USA.
Vaziri
N D
ND
Wang
X Q
XQ
Barnard
R J
RJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015415:Biomarkers; D001794:Blood Pressure; D001835:Body Weight; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000209:etiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D015415:Biomarkers; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester