Introduction: 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.

High fructose diet increases renal reactive oxygen species (ROS) production which enhances renal sodium reabsorption and renin secretion, thereby increasing extracellular volume and vasoconstriction. With concurrent high sodium consumption, hypertension occurs prior to the development of frank metabolic syndrome. Prolonged hypertension causes vascular dysfunction by reducing compliance, leading to end‐organ damage to the heart and kidneys. Daily treatment with Tempol®, a ROS scavenger, prevents increases in mean arterial pressure (MAP) associated with a fructose and high salt (FHS) diet, indicating a pathologic role of ROS in this model. We hypothesized that daily administration of Tempol® ameliorates the reduction in vascular compliance and abnormalities in cardiac function associated with FHS induced hypertension. Male Sprague‐Dawley rats were fed either 20% glucose or 20% fructose in drinking water with normal (0.4%) salt chow for one week followed by 3 weeks of normal or high (4.0%) salt chow. Half of each group was supplemented with Tempol®, 15 mg/400 g body weight daily in drinking water, beginning at one week after fructose or glucose feeding. Hemodynamics were monitored by telemetry. Ultrasonography was performed under isoflurane anesthesia. The change in MAP from baseline in the FHS group was significantly elevated compared with controls (4.98 vs. 0.16 mmHg, respectively; P < 0.01), and Tempol® administration prevented this increase. Despite increased MAP, plasma renin activity in FHS rats was not suppressed. Ultrasonography revealed significantly decreased aortic compliance, measured by pulse wave velocity (P < 0.01), and significantly increased renal resistive index (RRI) in the FHS group compared to glucose controls (P < 0.05). Tempol® administration reversed the increase in pulse wave velocity but had no effect on RRI. Systolic left ventricular function by echocardiographic assessment did not change but diastolic function was impaired. This was evidenced by decreased ratio of early to late transmitral filling velocity (P < 0.01). Tempol® did not restore mitral flow patterns to control levels. These findings indicate that the decrease in vascular compliance associated with FHS diet in male rats is, at least in part, mediated by oxidative stress. Other mechanisms seem to be at play in mediating the abnormal renovascular changes. Support or Funding Information VA Merit Award (RX000851) awarded to Noreen F. Rossi, MD. Peter Levanovich is supported in part by the Detroit Cardiovascular Training Program (NIH T32: HL 120822)