Fructose‐induced salt‐sensitive hypertension increases aortic stiffness and induces changes in systemic and renal hemodynamics

Abstract

When high fructose consumption is accompanied by high salt consumption, such as occurs in a typical Western diet, hypertension ensues and the exact mechanism still remains to be identified. Although it has been shown that at least part of the mechanism involves sodium retention by the small intestine and the proximal tubule of the kidney, and reduced renal nitric oxide production, the full spectrum of mechanisms of fructose‐induced salt‐sensitive hypertension and its impact on cardiovascular co‐morbidities remains unknown. The objective of this work was to delineate the longitudinal changes in systemic and renal hemodynamics as a consequence of fructose‐ and salt‐enriched diet. Our central hypothesis is that elevated fructose in the diet predisposes to salt‐sensitive hypertension and initiates changes in both renal and systemic hemodynamics. Previously we found that rats fed 20% fructose for one week develop salt sensitive hypertension within two weeks of high‐salt feeding (4% NaCl). In the present work, using echocardiography we found that fructose‐fed rats displayed increased stroke volume (190.1 ± 9.4 μL vs 145.7 ± 5.8 μL, p < 0.05) and increased left ventricular mass index (1.03 ± 0.06 vs 0.75 ± 0.06), while relative wall thickness remained unchanged. These results are indicative of left ventricular remodeling consistent with eccentric hypertrophy. This is further corroborated by diastolic diameter (6.8 ± 0.2 mm vs 5.9 ± 0.3 mm). Fructose‐fed rats on a high salt (F+HS) diet showed signs of increased aortic stiffness, since the distention to vasodilator phenylephrine was reduced in the ascending aorta (7.1 ± 1.0% from baseline vs 18.2 ± 1.3% from baseline, p<0.05) for the same increase in blood pressure, a result that was not observed in fructose fed rats that were on an normal salt diet (F+NS; 16.1± 2.9%, p < 0.05 vs F+HS). The observed increase in stiffness in the ascending aorta of F+HS rats is likely due to an increase in collagen deposition compared to F+NS and control rats. Finally, we wanted to determine whether the changes in systemic hemodynamics and parameters of cardiac function were paralleled by changes in renal hemodynamics. We measured renal resistive index (RRI) using ultrasound and found that it was elevated in F+HS rats compared to F+NS and control rats. Taken together, these results point to the apparent role of dietary fructose in inducing salt‐sensitive hypertension that is accompanied by increased aortic stiffness and concomitant changes in systemic and renal hemodynamics.Support or Funding InformationVA Merit Award to N.F.R.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.