Chronic etanercept treatment prevents the development of hypertension in fructose-fed rats.
The purpose of this study was to investigate the effect of chronic treatment with etanercept (a soluble recombinant fusion protein consisting of the extracellular ligand-binding domain of tumor necrosis factor receptor type 2) on the development of hypertension in fructose-fed rats (FFR). High fructose feeding and treatment with etanercept (0.3 mg/kg, three times per week) was initiated simultaneously in male Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin sensitivity, vascular reactivity, plasma angiotensin II (Ang II), and norepinephrine were determined following 9 weeks of treatment. FFR exhibited insulin resistance, hyperinsulinemia, hypertriglyceridemia, endothelial dysfunction, and hypertension. Treatment with etanercept prevented the rise in blood pressure without affecting insulin levels, insulin sensitivity, triglycerides, or Ang II levels in FFR. Etanercept treatment improved acetylcholine-induced relaxation and normalized endothelial nitric oxide synthase expression in aortas from FFR. The results of this study suggest that treatment with etanercept prevented the development of hypertension by improving vascular function and restoring endothelial nitric oxide synthase expression in FFR.
Division of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.
Linda T
LT
Tran
Kathleen M
KM
MacLeod
John H
JH
McNeill
D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D000068800:Etanercept; D005632:Fructose / Q000008:administration & dosage*; D006946:Hyperinsulinism; D006973:Hypertension / Q000188:drug therapy / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D005632:Fructose; D052250:Nitric Oxide Synthase Type III; D000068800:Etanercept