Defective endothelium-dependent relaxation in fructose-hypertensive rats.
The present study examined the endothelium-dependent and -independent responses of isolated mesenteric arteries to acetylcholine and the endothelium-independent vasodilator sodium nitroprusside in mesenteric arteries from fructose-induced hypertensive rats. Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when compared to controls (plasma insulin, 5.9 +/- 0.4 v control 3.6 +/- 0.4 ng/mL, P < .05; systolic blood pressure, 154 +/- 5 v control 127 +/- 7 mm Hg, P < .05). The maximum contractile response of mesenteric arteries to norepinephrine did not differ between the control and fructose groups, either with or without the endothelium. In arteries with intact endothelia, precontracted with the approximate ED50 of norepinephrine, the percent maximum relaxation produced by acetylcholine in hypertensive rats was lower than the control arteries (62 +/- 7 v control 95 +/- 5, P < .05) without any change in sensitivity. In arteries precontracted with norepinephrine, the endothelium-independent vasodilator sodium nitroprusside produced a dose-dependent relaxation in arteries obtained from control and fructose groups, both with and without the endothelium. The maximum relaxation produced by sodium nitroprusside did not differ between control and fructose arteries, either with or without the endothelium; however, removal of the endothelium caused an increase in sensitivity of this agonist. These data suggest that in the insulin resistant and hyperinsulinemic fructose-hypertensive rats, there is a defective endothelium-dependent yet preserved endothelium-independent relaxation.
Verma
S
S
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Bhanot
S
S
Yao
L
L
McNeill
J H
JH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005632:Fructose / Q000633:toxicity*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D009599:Nitroprusside; D005632:Fructose; D009569:Nitric Oxide; D000109:Acetylcholine