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(Hypertension. 2001;38:872.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Chronic Thromboxane Synthase Inhibition Prevents Fructose-Induced Hypertension

Denise Galipeau; Emi Arikawa; Inna Sekirov; John H. McNeill

From the Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

Correspondence to John H. McNeill, PhD, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, British Columbia, Canada, V6T 1Z3. E-mail jmcneill{at}interchange.ubc.ca

Abstract—— To investigate the role of thromboxane A₂ in the development of hypertension in the fructose-fed rat, we treated male fructose-fed rats with dazmegrel (a thromboxane synthase inhibitor) and monitored blood pressure, fasting plasma parameters, and insulin sensitivity for 7 weeks. Systolic blood pressure was measured each week using tail plethysmography, and an oral glucose tolerance test was performed at the end of the study to assess insulin sensitivity. Treatment with a 60% fructose diet and dazmegrel (100 mg · kg^-1 · d^-1 via oral gavage) was initiated on the same day. Plasma triglyceride levels increased 2-fold in both fructose- and fructose/dazmegrel-treated groups, and plasma insulin levels tended to be higher in these groups, although not significantly. Systolic blood pressure increased significantly throughout the study in the fructose-fed group only (132±3 versus 112±4 mm Hg in control rats, 118±2 mm Hg in control-treated rats, 116±2 mm Hg in fructose-treated rats). Both fructose groups demonstrated a higher peak insulin response to oral glucose challenge and had 40% to 60% lower insulin sensitivity index values. The results of this study show that treatment with a thromboxane synthase inhibitor, dazmegrel, can prevent the development of hypertension but does not improve insulin sensitivity or other fructose-induced metabolic impairments. Based on these data, we conclude that the potent vasoconstrictor thromboxane is involved in the link between hyperinsulinemia/insulin resistance and hypertension.

Key Words: insulin • thromboxane • blood pressure • rats, inbred strains • fructose • endothelin-1

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