Fructose-induced insulin resistance and hypertension in rats.

Abstract

SUMMARY To determine if hypertension could be produced in normal rats by feeding them a fructose-enriched diet, Sprague-Dawley rats were fed either normal chow or a diet containing 66% fructose as a percentage of total calories for approximately 2 weeks. At the end of this period systolic blood pressure had increased from 124 ± 2 to 145 ± 2 (SEM) mm Hg in the fructose-fed rats, whereas no change occurred in the control group. In addition, hyperinsulinemia and hypertriglyceridemia were associated with hypertension in fructose-fed rats. The addition of clonidine to the drinking water inhibited fructose-induced hypertension, but not the increase in plasma insulin or triglyceride concentration seen in fructose-fed rats. Thus, the metabolic changes associated with fructose-induced hypertension are unlikely to be secondary to an increase in sympathetic activity. Whether or not this is also true of the hypertension remains to be clarified. IT has been apparent for some time that increases in dietary carbohydrate intake can raise blood pressure in experimental animals. '• 2 In particular, the ability of sucrose feeding to accentuate the magnitude of the blood pressure elevation already present in spontaneously hypertensive rats has been documented. 3 " 3 Since sucrose feeding stimulates sympathetic nervous system activity, 6 it has been suggested that sucroseinduced increases in sympathetic activity may elevate blood pressure in susceptible animals.4 Indirect support for this hypothesis was provided by the observation that rats with sucrose-induced hypertension had faster heart rates and larger hypotensive responses to a-adrenergic blockade with phentolamine than did their normotensive controls.7 This point of view has recently received added support from the demonstration that hypertension produced by sucrose feeding is associated with evidence of increased catecholamine Received March 13, 1987; accepted June 21, 1987. secretion. 5 However, the physiological effects of sucrose are not limited to an increase in sympathetic activity, and rats fed a high sucrose diet also become insulin-resistant and hyperinsulinemic.8 ' 9 Since several recent observations have documented an association between hyperinsulinemia and hypertension in humans, 10 " 12 it seemed important to see if a similar phenomenon could be found in carbohydrate-induced hypertension in rats. Thus, the current study was initiated to address this issue, and we have taken a somewhat different approach than has been conventionally used in an effort to broaden the nature of inquiry. First, we used normal Sprague-Dawley rats, not animals with spontaneous hypertension, to see if high carbohydrate diets can induce hypertension in rats with no apparent genetic propensity to become hypertensive. Second, we used fructose, not sucrose, as the source of dietary carbohydrate. Fructose feeding can also cause insulin resistance and hyperinsulinemia in normal rats.'14 If fructose also produces hypertension, it would suggest that the insulin resistance and hyperinsu...

Parasympathetic dysfunction is associated with insulin resistance in fructose-fed female rats

“…An association between hyperinsulinemia and hypertension in humans and animals has been demonstrated (4,7). However, the role of the autonomic nervous system in metabolic and cardiovascular dysfunctions induced by high fructose diet is not well understood, mainly regarding Vagal dysfunction in fructose-fed female rats www.bjournal.com.br the female gender (5,6,8).…”

“…Consumption of large quantities of fructose by humans and animals leads to insulin resistance, lipid abnormalities, obesity, hypertension and renal dysfunction (1)(2)(3)(4)(5). The cluster of these metabolic alterations, which are related to increased cardiovascular risk, is known as metabolic syndrome, and has reached epidemic levels in the world (1).…”

“…Previous studies demonstrated that a high fructose intake in experimental animals leads not only to metabolic alterations, but also to cardiovascular, renal and autonomic dysfunction that are frequently accompanied by activation of sympathetic and renin-angiotensin systems (2)(3)(4)(5)(6)). An association between hyperinsulinemia and hypertension in humans and animals has been demonstrated (4,7).…”

“…Animals were anesthetized with thiopental (40 mg/kg body weight, ip), and a drop of blood from the tail was collected to measure blood glucose by using a glucosimeter (ACCU-CHEK). This procedure was performed at 0 time, 4,8,12, and 16 min after insulin administration (0.75 U/kg). The rate constant for blood glucose disappearance (KITT) was calculated using the formula 0.693/t1/2, and the blood glucose half-time (t1/2) was calculated from the slope of the least squares regression of the blood glucose concentration during the linear phase of decline (9).…”

Hypertension, single sugars and fatty acids

“…The introduction of fructose induces, within 10-15 days, insulin resistance, compensatory hyperinsulinaemia and a rise in blood pressure. 8,9 The introduction of glucose or sucrose in the diet without increase in total caloric intake during 2 weeks induces an increase in serum insulin without change in blood glucose, an increase in serum triglycerides and blood pressure, the latter being higher after sucrose. 10 The hypertensive effect of fructose has even been shown to be higher in rats with spontaneous hypertension.…”