Androgens Are Necessary for the Development of Fructose-Induced Hypertension

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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.