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Dragana Komnenov,1 Peter E Levanovich,2 Natalia Perecki,1 Charles S Chung,2 Noreen F Rossi1– 3 1Department of Internal Medicine, Division of Nephrology, Wayne State University School of Medicine, Detroit, MI, USA; 2Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA; 3Department of Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, MI, USACorrespondence: Noreen F RossiDepartment of Internal Medicine, Division of Nephrology, Wayne State University School of Medicine, 4160 John R Street #908, Detroit, MI 48201, USAEmail nrossi@wayne.eduIntroduction: High fructose and salt consumption continues to be prevalent in western society. Existing studies show that a rat model reflecting a diet of fructose and salt consumed by the upper 20th percentile of the human population results in salt-sensitive hypertension mitigated by treatment with an antioxidant. We hypothesized that dietary fructose, rather than glucose, combined with high salt leads to aortic stiffening and decreased renal artery compliance. We also expect that daily supplementation with the antioxidant, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (+T; Tempol), will ameliorate the increase in mean arterial pressure (MAP) and vascular changes.Methods: Male Sprague Dawley rats were studied with either 20% fructose or 20% glucose in the drinking water and normal salt (0.4%) or high salt (4%) in the chow resulting in four dietary groups: fructose normal Fru+NS or high salt (Fru+HS) or glucose with normal (Glu+NS) or high salt (Glu+HS). Tempol (+T) was added to the drinking water in half of the rats in each group for 3 weeks.Results: MAP was significantly elevated and the glucose:insulin ratio was depressed in the Fru+HS. Both parameters were normalized in Fru+HS+T. Plasma renin activity (PRA) and kidney tissue angiotensin II (Ang II) were not suppressed in the high salt groups. Pulse wave velocity (PWV), radial ascending strain, and distensibility coefficient of the ascending aorta were significantly decreased in Fru+HS rats and improved in the Fru+HS+T rats. No differences occurred in left ventricular systolic function, but the ratio of early (E) to late (A) transmitral filling velocities was decreased and renal resistive index (RRI) was higher in Fru+HS rats; antioxidant treatment did not change these indices.Discussion: Thus, short-term consumption of high fructose plus high salt diet by rats results in modest hypertension, insulin resistance, diminished aortic and renal artery compliance, and left ventricular diastolic dysfunction. Antioxidant treatment ameliorates the blood pressure, insulin resistance and aortic stiffness, but not renal artery stiffness and left ventricular diastolic dysfunction.Keywords: angiotensin II, hypertension, insulin resistance, pulse wave velocity, renin