We demonstrated that the
fructose-induced hypertensive rat, representative of the principal metabolic abnormalities found in a majority of hypertensive patients, i.e.
hypertriglyceridemia,
hyperinsulinemia and
insulin resistance (Syndrome X), is associated with an impaired response to
endothelium-dependent vasodilators and that
fructose may directly contribute to this impairment. Twelve male Wistar rats were divided into two groups, one given 10%
fructose (n=6); the other no
fructose (n=6) for 40 days in the
drinking water. Systolic blood pressure was measured via the tail cuff method. Perfusion pressure responses to
acetylcholine, were measured in the isolated perfused mesenteric vascular bed. Constrictor or dilator responses were measured as increases or decreases, respectively, of the perfusion pressure at a constant flow (4 ml/min).
Fructose-fed rats had significantly higher blood pressure,
insulin and
triglyceride levels than control animals. In
phenylephrine constricted beds, the endothelium-dependent dilatation to
acetylcholine (0.001 to 1 micromol) was attenuated in the
fructose-fed group compared to control animals. Whether this abnormality results from the syndromes (
hyperinsulinemia,
hypertension and
hypertriglyceridemia) associated with the
fructose-fed animal model is unknown. We therefore hypothesized that
fructose can impair the endothelium-dependent
vasodilator response. This was evaluated by perfusing mesenteric arteries from normal rats with control
mannitol (40 mM) or
fructose (40 mM). Endothelium-dependent dilation to
acetylcholine was impaired in
fructose-perfused mesenteric arteries.
Indomethacin restored the
vasodilator response to
acetylcholine, suggesting that a
cyclooxygenase derivative mediates the impaired response. Thus, we conclude that
fructose can contribute to the impaired endothelium-dependent response in the
fructose-induced hypertensive rat model.