Dietary fructose and high salt in young male Sprague Dawley rats induces salt‐sensitive changes in renal function in later life

Abstract

Dietary fructose and salt are associated with hypertension and renal disease. Dietary input during critical postnatal periods may impact pathophysiology in maturity. The highest consumption of fructose occurs during adolescence. We hypothesized that a diet high in fructose with or without high salt in young male Sprague Dawley rats will lead to salt‐sensitive hypertension, albuminuria, and decreased renal function in maturity. Four groups were studied from age 5 weeks: 20% glucose + 0.4% salt (GCS‐GCS) or 20% fructose + 4% salt throughout (FHS‐FHS). Two groups received 20% fructose + 0.4% salt or 20% fructose + 4% salt for 3 weeks (Phase I) followed by 20% glucose + 0.4% salt (Phase II). In Phase III (age 13–15 weeks), these two groups were challenged with 20% glucose + 4% salt, (FCS‐GHS) and (FHS‐GHS), respectively. Each group fed fructose in Phase I exhibited significantly higher MAP than GCS‐GCS in Phase III. Net sodium balance, unadjusted, or adjusted for caloric intake and urine flow rate, and cumulative sodium balance were positive in FHS during Phase I and were significantly higher in FCS‐GHS, FHS‐GHS, and FHS‐FHS vs GCS‐GCS during Phase III. All three groups fed fructose during Phase I displayed significantly elevated albuminuria. GFR was significantly lower in FHS‐FHS vs GCS‐GCS at maturity. Qualitative histology showed mesangial expansion and hypercellularity in FHS‐FHS rats. Thus, fructose ingestion during a critical period in rats, analogous to human preadolescence and adolescence, results in salt‐sensitive hypertension and albuminuria in maturity. Prolonged dietary fructose and salt ingestion lead to a decline in renal function with evidence suggestive of mesangial hypercellularity.

Longitudinal Associations of Dietary Fructose, Sodium, and Potassium and Psychological Stress with Vascular Aging Index and Incident Cardiovascular Disease in the CARDIA Cohort

“…Indeed, pre-clinical work showed that even a short-term moderate increase in dietary fructose causes salt-sensitive blood pressure, diastolic dysfunction, and increased aortic PWV in rats [ 29 , 30 , 31 , 32 ]. Additionally, other rodent models showed that the increased ingestion of fructose and salt during early age (i.e., equivalent to adolescence in humans), contributes to hypertension, vascular stiffness, and a decrease in glomerular filtration rate (GFR) later in life even after the exposure to fructose and salt had been removed and later re-introduced to rats once they were older (i.e., equivalent to mid-life in humans) [ 33 , 34 ]. Likewise, in a systematic review and meta-analysis of six human cohort studies, sugar-sweetened beverages were significantly associated with an increased risk of hypertension, although vascular aging variables were not measured [ 35 ].…”

Acute Intake of Fructose Increases Arterial Pressure in Humans: A Meta-Analysis and Systematic Review

“…Similar findings have been observed in resistance vessels [ 83 ] but diminished vasodilatory capacity could also contribute to fructose-induced elevations in blood pressure. Hypertension may be further exacerbated since fructose appears to impart salt sensitivity, meaning that urinary sodium excretion is impaired with fructose intake of roughly 20% of total calories [ 12 , 84 ]. High salt intake increases endogenous hepatic fructose generation [ 85 ].…”

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort

“…Studies completed on animals showed that even moderate increases in dietary fructose and sodium in the short-term result in elevated blood pressure at least partially via increased sympathetic tone, as well as the development of diastolic dysfunction and increased aortic stiffness [6][7][8]. Other rodent models showed that an increased ingestion of fructose and salt at an early age (i.e., equivalent to adolescence in humans) increased blood pressure, vascular stiffness and decreased glomerular filtration rate (GFR) later in life even after the exposure to fructose and salt had been removed and later re-introduced to rats once they were older (i.e., equivalent to mid-life in humans) [9,10]. Several human cohort studies have highlighted that dietary fructose contributes to obesity, insulin resistance and dyslipidemia, all of which are expected to impair cardiometabolic health [11].…”