Figure 2:

Proposed pathogenic mechanism for how fructose could cause primary hypertension. Fructose can be provided directly in the diet (such as from added sugars) or endogenously produced via the polyol pathway from high glycemic foods that provide the substrate, or from high-salt diet or uric acid (from umami foods) that stimulate aldose reductase, the rate-limiting enzyme that converts the glucose to fructose. The net effect of fructose metabolism and elevated intracellular uric acid is the activation of a “survival switch” that drives multiple metabolic responses. However, included in this response is an increase in salt absorption by the gut and kidney, a rise in leptin that activates sympathetic central nervous system, a stimulation of vasopressin with its vasoconstrictive properties, and a uric acid–dependent stimulation of the renin–angiotensin–aldosterone system (RAAS), the stimulation of oxidative stress and a fall in endothelial nitric oxide (NO) availability. Systemic and renal vasoconstriction follow with a rise in blood pressure. Initially this is labile and intermittent, but over time the recurrent ischemia to the kidney stimulates the expression of de novo antigens, HSP70, that induce an autoimmune response that maintains the renal vasoconstriction and elevated blood pressure. The renal vasoconstriction then results in impaired sodium excretion, leading to a rise in salt concentration and a reactivation of the pathway via a positive feedback system which helps maintain the elevation in blood pressure. Other factors, including genetic and congenital factors, can influence this pathway.