Abstract-Placental insufficiency in the rat results in intrauterine growth restriction and development of hypertension in prepubertal male and female growth-restricted offspring. However, after puberty, only male growth-restricted offspring remain hypertensive, whereas female growth-restricted offspring stabilize their blood pressure to levels comparable to adult female controls. Because female rats reach their maximum levels of estrogen at puberty, we hypothesize that estrogen may be a factor involved in the stabilization of blood pressure in adult female growth-restricted offspring. At 10 weeks of age, female control and growth-restricted offspring underwent ovariectomy or sham surgery and insertion of a telemetry probe. Mean arterial pressure was similar at 16 weeks of age between control (123Ϯ4 mm Hg) and growth-restricted offspring (122Ϯ2 mm Hg); however, ovariectomy led to a significant increase in blood pressure in growth-restricted offspring (140Ϯ2 mm Hg; PϽ0.05 versus intact counterpart) with no significant effect in controls (124Ϯ1 mm Hg). Estrogen replacement by subcutaneous minipellet initiated at 14 weeks of age in a subset of ovariectomized control and growth-restricted offspring reversed the effect of ovariectomy on blood pressure in growth-restricted offspring at 16 weeks of age (111Ϯ3 mm Hg; PϽ0.05 versus ovariectomized counterpart); renin angiotensin system blockade also abolished ovariectomy-induced hypertension in female growth-restricted offspring (106Ϯ2 mm Hg; PϽ0.05 versus ovariectomized counterpart). Therefore, sex differences are observed in this model of fetal programmed hypertension, and results from this study suggest that estrogen contributes to normalization of blood pressure in adult female growth-restricted offspring. Key Words: fetal programming Ⅲ intrauterine growth restriction Ⅲ ovariectomy Ⅲ estrogen Ⅲ renin angiotensin system H ypertension shows a clear age-related sex dimorphism. Nearly 1 in 3 adult Americans have hypertension. A higher percentage of men than women have hypertension until age 45 years, the percentage is similar from ages 45 to 54 years, and it becomes higher for women after that. 1 Thus, the risk of hypertension increases in women after the onset of menopause and continues to rise with age. 1-4 As a result, after menopause, a greater percentage of women have hypertension than age-matched men. 1,5,6 Epidemiological evidence suggests a regulatory role for estrogens in maintaining vascular function and structure. 7-9 Loss of ovarian function results in estrogen deficiency and increased risk for development of cardiovascular diseases, such as hypertension in postmenopausal women and women with ovarian surgical ablation. [7][8][9][10] In animal models of hypertension in which female rats are normotensive relative to their hypertensive male counterparts, ovariectomy induces hypertension. 11-14 Therefore, it seems that, while the ovaries are functional, women have a lower risk of cardiovascular disease than men, an observation supported by experimental studies.Alte...
