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.
Similar content being viewed by others
Article PDF
References
Cavarape A, Feletto F, Mercuri F, Quagliaro L, Daman G, Ceriello A : High-fructose diet decreases catalase mRNA levels in rat tissues. J Endocrinol Invest 2001; 24: 838–845.
Nyby MD, Matsumoto K, Yamamoto K, et al: Dietary fish oil prevents vascular dysfunction and oxidative stress in hyperinsulinemic rats. Am J Hypertens 2005; 18: 213–219.
Busserolles J, Gueux E, Rock E, Demigne C, Mazur A, Rayssiguier Y : Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J Nutr 2004; 133: 1903–1908.
Shinozaki K, Ayajiki K, Nishio Y, Sugaya T, Kashiwagi A, Okamura T : Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance. Hypertension 2004; 43: 255–262.
Bell RC, Carlson JC, Storr KC, Herbert K, Sivak J : High-fructose feeding of streptozotocin-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney. Br J Nutr 2000; 84: 575–582.
Taniyama Y, Griendling KK : Reactive oxygen species in the vasculature. Molecular and cellular mechanisms. Hypertension 2002; 42: 1075–1081.
Miatello R, Risler N, Castro C, Gonzalez S, Ruttler M, Cruzado M : Aortic smooth muscle cell proliferation and endothelial nitric oxide synthase in fructose-fed rats. Am J Hypertens 2001; 14: 1135–1141.
Sowers JR : Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol 2004; 286: H1597–H1602.
Tuck ML, Bounoua F, Eslami P, Nyby MD, Eggena P, Corry DB : Insulin stimulates endogenous angiotensin II production via a mitogen-activated protein kinase pathway in vascular smooth muscle cells. J Hypertens 2004; 22: 1779–1785.
Kamide K, Hori MT, Zhu J, Barrett JD, Eggena P, Tuck ML : Insulin-mediated growth in aortic smooth muscle and vascular renin-angiotensin system. Hypertension 1998; 32: 482–487.
Miatello R, Risler N, Gonzalez S, Castro C, Ruttler M, Cruzado M : Effects of enalapril on the vascular wall in an experimental model of syndrome X. Am J Hypertens 2002; 15: 872–878.
Hsieh PS, Tai YH, Loh CH, Shih KC, Cheng WT, Chu CH : Functional interaction of AT1 and AT2 receptors in fructose-induced insulin resistance and hypertension in rats. Metabolism 2005; 54: 157–164.
Takagawa Y, Berger ME, Tuck ML, Golub MS : Impaired endothelial alpha-2 adrenergic receptor–mediated relaxation in the fructose-fed rat. Hypertens Res 2002; 25: 197–202.
Xu Z-G, Lanting L, Vaziri N, et al: Upregulation of angiotensin II type 1 receptor, inflammatory mediators, and enzymes of arachidonate metabolism in obese Zucker rat kidney. Circulation 2005; 111: 1962–1969.
D'Angelo G, Elmarakby AA, Pollock DM, Stepp DW : Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats. Hypertension 2005; 46: 806–811.
Shimamoto K, Ura N, Nakagawa M, et al: The mechanisms of the improvement of insulin sensitivity by angiotensin converting enzyme inhibitor. Clin Exp Hypertens 1996; 18: 257–266.
Chen S, Kashiwabara H, Kosegawa I, Ishii J, Katayama S : Bradykinin may not be involved in improvement of insulin resistance by angiotensin converting enzyme inhibitor. Clin Exp Hypertens 1996; 18: 625–636.
Wingler K, Wunsch S, Kreutz R, Rothermund L, Paul M, Schmidt MM : Upregulation of the vascular NAD(P)H-oxidase isoforms Nox1 and Nox4 by the renin-angiotensin system in vitro and in vivo. Free Radic Biol Med 2001; 31: 1456–1464.
Yagi S, Morita T, Katayama S : Combined treatment with an AT1 receptor blocker and angiotensin converting enzyme inhibitor has an additive effect on inhibiting neointima formation via improvement of nitric oxide production and suppression of oxidative stress. Hypertens Res 2004; 27: 129–135.
Fujiwara T, Saitoh S, Takagi S, et al: Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia. Hypertens Res 2005; 28: 665–670.
Luvara G, Pueyo ME, Philippe M, et al: Chronic blockade of NO synthase activity induces a proinflammatory phenotype in the arterial wall: prevention by angiotensin II antagonism. Arterioscler Thromb Vasc Biol 1998; 18: 1408–1416.
Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB : Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor–kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 2000; 20: 645–651.
Toba H, Nakagawa Y, Miki S, et al: Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the NG-nitro-L-arginine methyl ester–induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure–lowering effects of amlodipine and manidipine. Hypertens Res 2005; 28: 689–700.
Iyer SN, Raizada MK, Katovich MJ : AT1 receptor density changes during development of hypertension in hyperinsulinemic rats. Clin Exp Hypertens 1996; 18: 793–810.
Hwang IS, Huang WC, Wu JN, Shian LR, Reaven GM : Effect of fructose-induced hypertension on the renin-angiotensin-aldosterone system and atrial natriuretic factor. Am J Hypertens 1989; 2: 424–427.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nyby, M., Abedi, K., Smutko, V. et al. Vascular Angiotensin Type 1 Receptor Expression Is Associated with Vascular Dysfunction, Oxidative Stress and Inflammation in Fructose-Fed Rats. Hypertens Res 30, 451–457 (2007). https://doi.org/10.1291/hypres.30.451
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.30.451
Keywords
This article is cited by
-
Plasticity in Motoneurons Following Spinal Cord Injury in Fructose-induced Diabetic Rats
Journal of Molecular Neuroscience (2022)
-
Role of activating transcription factor 3 in fructose-induced metabolic syndrome in mice
Hypertension Research (2018)
-
Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats
Hypertension Research (2016)
-
Effects of Lesions to Capsaicin-Sensitive Nerves on Blood Pressure in Metabolic Syndrome in Rats
Neuroscience and Behavioral Physiology (2015)
-
Supplementary Chromium(III) Propionate Complex Does Not Protect Against Insulin Resistance in High-Fat-Fed Rats
Biological Trace Element Research (2014)