Vascular Angiotensin Type 1 Receptor Expression Is Associated with Vascular Dysfunction, Oxidative Stress and Inflammation in Fructose-Fed Rats

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.