EFFECT OF ESTROGEN WITHDRAWAL ON BLOOD-PRESSURE AND INSULIN-RESISTANCE IN SUCROSE-FED JUVENILE RATS

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insul in resistance and hypertension. These conditions develop despite the a bsence of genetic predisposition to either. When studied with the eugl ycemic hyperinsulinemic clamp technique, these rats have reduced insul in-stimulated glucose utilization, but normal suppression of hepatic g lucose output. In the young sucrose-fed rats, it was noted that the de gree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen wi thdrawal increases insulin resistance and hypertension. Female rats we re randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect ta il-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthes ia and uterine horn exposure without removal of the ovaries). At 13 to 14 weeks of life, all animals were fasted overnight, and had an oral glucose tolerance test while conscious. Weight and weight gain were no t different among the groups over the 11 week study period. Animals fe d the sucrose diet developed significantly higher blood pressure than animals fed the control diet; oophorectomized animals had higher blood pressure than sham-operated animals (P <.0001). Sucrose-fed oophorect omized animals developed fasting and glucose-stimulated hyperinsulinem ia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withd rawal in these animals also induces fasting and glucose-stimulated hyp erinsulinemia, which are signs of worsening insulin resistance. Androg en:estrogen imbalance increases metabolic dysfunction and worsens hype rtension in this animal model. (C) American Journal of Hypertension, L td.