The Relation between Fructose-Induced Metabolic Syndrome and Altered Renal Haemodynamic and Excretory Function in the Rat

Abstract

This paper explores the possible relationships between dietary fructose and altered neurohumoral regulation of renal haemodynamic and excretory function in this model of metabolic syndrome. Fructose consumption induces hyperinsulinemia, hypertriglyceridaemia, insulin resistance, and hypertension. The pathogenesis of fructose-induced hypertension is dubious and involves numerous pathways acting both singly and together. In addition, hyperinsulinemia and hypertension contribute significantly to progressive renal disease in fructose-fed rats. Moreover, increased activity of the renin-angiotensin and sympathetic nervous systems leading to downregulation of receptors may be responsible for the blunted vascular sensitivity to angiotensin II and catecholamines, respectively. Various approaches have been suggested to prevent the development of fructose-induced hypertension and/or metabolic alteration. In this paper, we address the role played by the renin-angiotensin and sympathetic nervous systems in the haemodynamic alterations that occur due to prolonged consumption of fructose.

Figure 1

The proposed mechanisms by which fructose feeding results in hypertension. BRA: baroreflex sensitivity; SNS: sympathetic nervous system; RAS: renin-angiotensin system.

Figure 2

(a) The effect of fructose-feeding on the renal vascular responses to adrenergic agonists and Ang II. The vascular responses, as assessed by the reduction in renal cortical blood flow (CBF) due to adrenergic agonists or Ang II intra-arterial administration (see methods), were significantly lower in fructose-fed (the gray square) compared to control (the white square) animals. (b) The effect of streptozotocin-induced diabetes on the renal vascular responses to adrenergic agonists and renal nerve stimulation. The vascular response to adrenergic stimuli as assessed by reduction in total renal blood flow (RBF) due to renal vasoconstriction was slightly lower although significant only for noradrenaline in diabetic (the gray square) compared to nondiabetic (the white square) rats. Figures are reproduced from Abdulla et al. [16] and Armenia et al. [144] respectively. Data, mean ± SEM represent the overall mean of responses to a range of doses from each agonist. Statistical analysis was performed by unpaired t-test for comparing between two groups each time, ∗ is P < 0.05 of fructose-fed versus control in (a) or diabetic versus nondiabetic in (b), (n = 6). NA: Noradrenaline; PE: phenylephrine; ME: methoxamine; RNS: renal nerve stimulation.

Figure 3

Proposed mechanisms that may explain the decreased vascular responses to vasoactive compounds in the fructose-fed rats. ↑ and ↓ stand for increase and decrease, respectively.