Fructose‐induced salt‐sensitive blood pressure differentially affects sympathetically mediated aortic stiffness in male and female Sprague‐Dawley rats

Abstract

Hypertension is the leading risk factor for major adverse cardiovascular events (MACE). Aortic stiffness and sympathoexcitation are robust predictors of MACE. Combined high fructose and sodium intake increases arterial pressure, aortic stiffness, renin, and sympathetic nerve activity in male rats. We hypothesized that activation of the renin angiotensin system (RAS) and/or the sympathetic system mediates aortic stiffness in rats with fructose‐induced salt‐sensitive blood pressure. Male and female Sprague‐Dawley rats ingested 20% fructose or 20% glucose in drinking water with 0.4% NaCl chow for 1 week. Then, fructose‐fed rats were switched to 4% NaCl chow (Fru + HS); glucose‐fed rats remained on 0.4% NaCl chow (Glu + NS, controls for caloric intake). After 2 weeks, mean arterial pressure (MAP) and aortic pulsed wave velocity (PWV) were evaluated at baseline or after acute intravenous vehicle, clonidine, enalapril, losartan, or hydrochlorothiazide. Baseline global longitudinal strain (GLS) was also assessed. MAP and PWV were greater in male Fru + HS versus Glu + NS male rats (p < 0.05 and p < 0.001, respectively). PWV was similar between the female groups. Despite similarly reduced MAP after clonidine, PWV decreased in Fru + HS versus Glu + NS male rats (p < 0.01). Clonidine induced similar decreases in MAP and PWV in females on either diet. GLS was lower in Fru + HS versus Glu + NS male rats and either of the female groups. Thus, acute sympathoinhibition improved aortic compliance in male rats with fructose salt‐sensitive blood pressure. Female rats retained aortic compliance regardless of diet. Acute RAS inhibition exerted no significant effects. Male rats on fructose high salt diet displayed an early deficit in myocardial function. Taken together, these findings suggest that adult female rats are protected from the impact of fructose and high salt diet on blood pressure, aortic stiffness, and early left ventricular dysfunction compared with male rats.

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

“…In fact, since the advent of HFCS in the 1970s, this has been the primary component of sugar used by the food industry in North America [ 28 ]. 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 ].…”

Knocking Out Sodium Glucose–Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension

“…However, others have reported that females are protected from the cardiovascular effects of dietary fructose. 56 There are at least 3 possible explanations for the discrepancy. First, the diets were significantly different.…”

“…Second, their rats were obtained from Harlan, while ours were from Charles River, and Sprague-Dawley rats from different sources have been shown to have different BPs 57 and different responses to environmental stimuli. 58 Finally, BP was measured under different conditions, that is, isoflurane anesthesia, 56 which may have impacted BP 59 versus awake animals.…”

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

“…Unfortunately, our search for studies in human subjects was only able to identify controlled studies reporting the acute effects of acute fructose ingestion (several hours). In contrast, animal studies showing deleterious effects on hemodynamics have largely assessed the long-term effects (weeks to months) of fructose on blood pressure [ 44 , 45 , 46 , 47 ], with some animal studies using dietary amounts exceeding what is typically ingested by people [ 36 , 37 , 38 , 39 ]. We identified only a limited number of publications reporting the direct effects of fructose on blood pressure in humans.…”

“…Notwithstanding, these changes occur despite normal blood glucose levels in the fructose-fed rats and do not elevate blood glucose levels [ 12 , 91 ]; however, insulin resistance was evident despite euglycemia [ 11 , 18 , 90 ]. Furthermore, a fructose-rich diet is associated with increased aortic stiffness in both rats [ 47 , 90 ] and humans [ 92 ]. Aortic stiffness is now recognized as a significant risk factor for cardiovascular disease and mortality [ 93 , 94 ].…”