Effect of estrogen withdrawal on blood pressure and insulin resistance in sucrose-fed juvenile rats

Abstract

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insulin resistance and hypertension. These conditions develop despite the absence of genetic predisposition to either. When studied with the euglycemic hyperinsulinemic clamp technique, these rats have reduced insulin-stimulated glucose utilization, but normal suppression of hepatic glucose output. In the young sucrose-fed rats, it was noted that the degree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen withdrawal increases insulin resistance and hypertension. Female rats were randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect tail-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthesia 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 not different among the groups over the 11 week study period. Animals fed 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 oophorectomized animals developed fasting and glucose-stimulated hyperinsulinemia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withdrawal in these animals also induces fasting and glucose-stimulated hyperinsulinemia, which are signs of worsening insulin resistance. Androgen:estrogen imbalance increases metabolic dysfunction and worsens hypertension in this animal model.