Fructose perfusion in rat mesenteric arteries impairs endothelium-dependent vasodilation.
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.
Richey
J M
JM
Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Si
X
X
Halter
J B
JB
Webb
R C
RC
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005632:Fructose / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D005632:Fructose; D000109:Acetylcholine