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. 2018 Jul 20;8(1):10970.
doi: 10.1038/s41598-018-29336-3.

The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations

Fernando Dos Santos  1 , Ivana C Moraes-Silva  2 , Edson D Moreira  2 , Maria-Claudia Irigoyen  2
Affiliations

The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations

Fernando Dos Santos et al. Sci Rep. .

Abstract

It is well-established that baroreflex sensitivity is essential for blood pressure control, and also plays a key role in the modulation of disease-induced metabolic alterations. In order to investigate the role of the baroreflex in the cardiometabolic and inflammatory derangements promoted by fructose overload, Wistar rats underwent sinoaortic denervation (SAD) or sham surgery and were studied 90 days after receiving tap water (Den and Ctrl) or a 10% fructose solution (Fruc and Den-Fruc). All experimental groups showed marked and similar degree of baroreflex impairment compared to Ctrl. As expected, fructose overload effectively induced metabolic syndrome; however, when it was associated with SAD, several alterations were attenuated. While Fruc rats displayed increased sympathetic modulation and tone and reduced vagal modulation compared to Ctrl animals, Den-Fruc rats showed greater vagal tone and modulation when compared to the Fruc group. Moreover, the Den-Fruc group showed augmented expression of β1 adrenergic receptors and TNF/IL-10 ratio and reduction of β2 in the left ventricle. The increase in vagal function was correlated with improved insulin sensitivity (r2 = 0.76), and decreased abdominal fat (r2 = -0.78) and β2 receptors (r2 = -0.85). Our results showed that: (1) chronic fructose overload induced severe baroreflex impairment, i.e. in a similar magnitude to that observed in SAD rats, which is accompanied by cardiometabolic dysfunctions; (2) the compensatory enhancement in parasympathetic function in SAD rats submitted to fructose intake may point out the possibility of use of approaches that improve vagal function as therapeutic target to attenuate fructose-induced cardiometabolic dysfunctions.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Autonomic blockade. Intrinsic heart rate (1A), sympathetic (1B) and vagal tone (1C) obtained by autonomic blockade with propranolol and methylatropine, respectively. Control (Ctrl), Fructose overload (Fruc), sinoaortic denervation (Den), and Den associated with fructose overload (Den-Fruc). *p < 0.05 vs. Ctrl; #p < 0.05 vs. Fruc by Bonferroni post-hoc, ANOVA (1A p = 0.240; 1B p = 0.006; 1C p = 0.018).
Figure 2
Figure 2
β Receptors expression. Quantification of β1 (2A) and β2 (2B) receptors in the left ventricle (LV). Percentage of change compared to control group. Control (Ctrl), Fructose overload (Fruc), sinoaortic denervation (Den), and Den associated with fructose overload (Den-Fruc). *p < 0.05 vs. Ctrl; #p < 0.05 vs. Fruc; $p < 0.05 vs. Den by Bonferroni post-hoc, ANOVA (2A p < 0.001; 2B p < 0.001).
Figure 3
Figure 3
Cardiac immunohistochemistry. Nuclear factor kappa B (NFκB) (3A) and interleukin-6 (IL-6) (3B) by immunohistochemistry in cardiac tissue. Control (Ctrl), Fructose overload (Fruc), sinoaortic denervation (Den), and Den associated with fructose overload (Den-Fruc). *p < 0.05 vs. Ctrl; #p < 0.05 vs. Fruc by Bonferroni post-hoc, ANOVA (3A p = 0.005; 3B p < 0.001).
Figure 4
Figure 4
Cardiac inflammation. Tumor necrosis factor alpha (TNFα) (4A) interleukin-10 (IL-10) (4B) and the TNFα/IL-10 ratio (4C) by ELISA in cardiac tissue. Control (Ctrl), Fructose overload (Fruc), sinoaortic denervation (Den), and Den associated with fructose overload (Den-Fruc). *p < 0.05 vs. Ctrl; #p < 0.05 vs. Fruc by Bonferroni post-hoc, ANOVA (4A p = 0.018; 4B p = 0.039; 4C p = 0.023).
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