title: Androgens are necessary for the development of fructose-induced hypertension.
abstract: Hyperinsulinemia and insulin resistance are closely associated with hypertension in humans and in animal models. Gender differences have been found in the development of hypertension in fructose-fed rats. The objectives of the present study were, first, to clarify whether androgens are required in the development of hyperinsulinemia, insulin resistance, and hypertension in fructose-fed rats, and second, to determine if cyclooxygenase-1 and cyclooxygenase-2 are also increased in the arteries of these rats. Male rats were gonadectomized or sham-operated and fed a 60% fructose diet beginning at age 7 weeks. Blood pressure was measured by a tail-cuff method, and an oral glucose tolerance test was performed to assess insulin sensitivity after 8 weeks of fructose feeding. Cyclooxygenase-1 and cyclooxygenase-2 mRNA expression was also assessed in the thoracic aortae and mesenteric arteries. Gonadectomy prevented hypertension from developing in the fructose-fed rats, but hyperinsulinemia and insulin resistance developed. There was an increase in cyclooxygenase-2 expression in the thoracic aortae and mesenteric arteries of the fructose-fed sham-operated rats while the expression of cyclooxygenase-1 remained unchanged. Gonadectomy prevented the mRNA overexpression of vascular cyclooxygenase-2 in the fructose-fed rats. These results suggest that the presence of androgens is necessary for the development of fructose-induced hypertension. Androgens apparently act as a link between hyperinsulinemia/insulin resistance and hypertension in fructose-hypertensive rats. Furthermore, an increase in the expression of cyclooxygenase-2 is implicated in the development of hypertension. The mechanisms involved require further study.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada. jmcneill@interchange.ubc.ca
authors.forename: Dongzhe
authors.initials: D
authors.lastname: Song
authors.forename: Emi
authors.initials: E
authors.lastname: Arikawa
authors.forename: Denise
authors.initials: D
authors.lastname: Galipeau
authors.forename: Mary
authors.initials: M
authors.lastname: Battell
authors.forename: John H
authors.initials: JH
authors.lastname: McNeill
mesh_terms: D000728:Androgens / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005632:Fructose; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000150:complications; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D001786:Blood Glucose; D007328:Insulin; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D005632:Fructose; D013739:Testosterone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat