FRUCTOSE PERFUSION IN RAT MESENTERIC-ARTERIES IMPAIRS ENDOTHELIUM-DEPENDENT VASODILATION

We demonstrated that the fructose-induced hypertensive rat, representa tive of the principal metabolic abnormalities found in a majority of h ypertensive patients, i.e. hypertriglyceridemia, hyperinsulinemia and insulin resistance (Syndrome X), is associated with an impaired respon se to endothelium-dependent vasodilators and that fructose may directl y 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 me asured via the tail cuff method. Perfusion pressure responses to acety lcholine, were measured in the isolated perfused mesenteric vascular b ed. Constrictor or dilator responses were measured as increases or dec reases, respectively, of the perfusion pressure at a constant flow (4 ml/min). Fructose-fed rats had significantly higher blood pressure, in sulin and triglyceride levels than control animals. In phenylephrine c onstricted beds, the endothelium-dependent dilatation to acetylcholine (0.001 to 1 mu mol) was attenuated in the fructose-fed group compared to control animals. Whether this abnormality results from the syndrom es (hyperinsulinemia, hypertension and hypertriglyceridemia) associate d with the fructose-fed animal model is unknown. We therefore hypothes ized that fructose can impair the endothelium-dependent vasodilator re sponse. This was evaluated by perfusing mesenteric arteries from norma l 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 t he impaired response. Thus, we conclude that fructose can contribute t o the impaired endothelium-dependent response in the fructose-induced hypertensive rat model. Published by Elsevier Science Inc.