<p>Aortic Stiffness and Diastolic Dysfunction in Sprague Dawley Rats Consuming Short-Term Fructose Plus High Salt Diet</p>

Abstract

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.

Fructose plus High-Salt Diet in Early Life Results in Salt-Sensitive Cardiovascular Changes in Mature Male Sprague Dawley Rats

“…PRA was not suppressed in the FCS-FHS and the FHS-FHS groups. Ideally, concurrent plasma Ang II measurements would have been confirmatory as in our previous studies [7,27]. The volume of plasma required for plasma Ang II measurements by validated assay in our laboratory is 0.8-1.0 mL.…”

“…However, increased extracellular volume is unlikely to be the only governing factor. Prolonged fructose feeding has been associated with hyperinsulinemia which can cause increased levels of other vasoactive factors such as endothelin-1 [ 28 ], reactive oxygen species and uric acid [ 4 , 27 , 44 , 45 , 46 , 47 ]. Although no differences in basal plasma glucose or insulin levels were observed among all four groups, the significantly lower glucose:insulin ratio in the groups that consumed fructose and high salt in adolescence indicates a possible role for insulin resistance, a hallmark of pre-diabetes.…”

“…The elevated RRI is thus consistent with the increased aortic PWV observed in this present study but suggests that the decline in renal artery compliance is delayed compared with changes in the ascending aorta and aortic arch where hydrostatic and shear forces are greater [ 59 ]. Oxidative stress [ 27 , 47 ], impaired nitric oxide generation [ 6 ], and inflammatory mechanisms [ 60 ] have been implicated in vascular changes during fructose and high-salt exposure. Again, whether these same factors contribute to the impaired compliance of the aorta and renal artery observed after exposure to fructose and high salt in youth is likely but remains to be proven.…”

“…Incorporating the carbohydrate in the chow permitted more accurate assessment of intake and equalization across groups. Nonetheless, it is important to note that, while the timeline of the study at present exceeds that of these prior studies, the values for hemodynamic, vascular, and cardiac parameters are comparable in our GCS-GCS rats that we used as reference group to parameters observed after three weeks of 20% glucose in drinking water with either 0.4% or 4% NaCl [ 27 ]. The 9- to 10-week exposure to dietary fructose in the FHS-FHS group was certainly longer than that in previous studies that evaluated these cardiovascular parameters.…”

“…Vascular Catheter Placement: At the end of Phase III and after the second ultrasonography study, catheters were placed into the left carotid artery and external jugular vein using ketamine and xylazine as above, and previously performed in our laboratory [ 7 , 27 ]. Catheters were secured with 3-0 silk suture and tunneled subcutaneously to the base of the neck and exteriorized.…”