title: Vascular Angiotensin type 1 receptor expression is associated with vascular dysfunction, oxidative stress and inflammation in fructose-fed rats.
abstract: This study determined whether or not oxidative stress and vascular dysfunction in fructose-induced hyperinsulinemic rats are associated with activation of the vascular renin-angiotensin system (RAS). Four groups of rats were used. CONT rats were fed normal rat chow, CONT+CAP were fed normal rat chow and given 500 mg/L captopril in their drinking water, fructose-fed rats (FFR) were fed a high-fructose diet and FFR+CAP were fed the high-fructose diet plus captopril in water. After 8 weeks, the vascular reactivity of mesenteric artery segments was measured. Blood was analyzed for insulin, glucose, hydrogen peroxide and 8-isoprostane. Aortic and heart tissue were used for subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Systolic blood pressure was significantly higher in FFR (p<0.05), and captopril treatment inhibited the blood pressure increase. Mesenteric artery dose-response curves to acetylcholine were shifted to the right in FFR (p<0.05) and were normal in FFR+CAP. Plasma insulin (p<0.05), hydrogen peroxide (p<0.02) and 8-isoprostane (p<0.05) were increased in FFR. Captopril treatment reducd hydrogen peroxide and 8-isoprostane concentrations. Aortic tissue mRNA expression levels were increased for angiotensin-converting enzyme (ACE, p<0.05), angiotensin type 1 receptor (AT1R, p<0.02), NOX4 (p<0.02) and VCAM-1 (p<0.05) in FFR aortic samples. Captopril treatment reduced AT1R, NOX4 and VCAM-1 expression in FFR to levels not different from CONT. Similar changes in heart tissue mRNA expression for angiotensinogen, AT1R and NOX4 were also observed. These results demonstrate that vascular RAS is upregulated in FFR and support the hypothesis that vascular RAS mediates vascular dysfunction and vascular oxidative stress in FFR.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. mnyby@ucla.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nyby
authors.forename: Karolin
authors.initials: K
authors.lastname: Abedi
authors.forename: Victoria
authors.initials: V
authors.lastname: Smutko
authors.forename: Pirooz
authors.initials: P
authors.lastname: Eslami
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tuck
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006973:Hypertension / Q000276:immunology* / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000276:immunology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D019010:Vascular Cell Adhesion Molecule-1; D005632:Fructose; D002216:Captopril; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat