ESTROGEN AMPLIFIES THE VASODILATION OF ANGIOTENSIN-(1-7)

目前，关于雌激素对健康的影响的信息有限。 高血压的发展和进展。增加的发病率 50岁后女性高血压的研究表明内分泌变化 与卵巢功能下降相关的因素在 高血压的发病机制及临床表现。这些问题 还没有得到充分的解决，目前还不清楚雌激素是否 对高血压有保护作用。毫无疑问，不止一个 系统在高血压的发病机制中起着重要作用。然而，在那里 是血管紧张素系统(RAS)的主要紊乱。我们演示了 在绝经后慢性激素替代模型中，雌激素 (E_2)均降低血管紧张素II(Ang II)的升压反应 增加Ang-(1-7)的降压作用。 此外，雌激素降低了血管紧张素转换酶(ACE)的mRNA。 肺、肾和主动脉，伴随着ACE活性的下降 在组织和血清中，并与循环减少有关 Ang II水平和Ang-(1-7)水平升高。这些发现 提供第一个证据，证明雌激素可能具有保护作用 通过改变血管收缩-血管扩张平衡来对抗高血压 RAS的成员。我们的假设是，雌激素有助于 调节动脉压增强局部区域 血管紧张素-(1-7)的扩血管作用及降低血管紧张素转换酶 血管紧张素Ⅱ的血管收缩作用--这一作用的关键成分 雌激素可能是通过下调血管紧张素而产生的 转化酶。我们将确定这些影响的机制 雌激素通过：1)测试雌激素是否增强局部血管扩张 血管对Ang-(1-7)的反应性；(2)测定雌激素是否 增加新的非AT1/非AT2的亲和力和数量 血管紧张素受体；3)确定雌激素是否改变局部 血管紧张素代谢；4)检测雌激素是否降低血管紧张素转换酶基因 通过经典的雌激素受体ERpha或新的雌激素 受体，ERbeta。这些新颖的研究将加深我们对 雌激素在促旁分泌和促性腺激素分泌中的作用 血管紧张素-(1-7)参与局部血管调节 耐药性，并可能为使用雌激素治疗 预防和治疗绝经后妇女的心血管疾病。

Presently, there is limited information on the effects of estrogen on the development and progression of hypertension. The increased incidence of hypertension in women after age 50 suggests that endocrine changes associated with a decline in ovarian function play a role in the pathogenesis and clinical manifestations of hypertension. These issues have not been adequately addressed, and it is not clear whether estrogen is protective in regard to hypertension. Unquestionably, more than one system plays a role in the pathogenesis of hypertension. However, there are major derangements in the angiotensin system (RAS). We demonstrated in a model of postmenopausal chronic hormone replacement that estrogen (E2) both reduced the pressor response to angiotensin II (Ang II) and increased the magnitude of the vasodepressor actions of Ang-(1-7). Further, estrogen reduced angiotensin converting enzyme (ACE) mRNA in lung, kidney, and aorta, in conjunction with a decrease in ACE activity in tissues and serum, and in association with a reduction in circulating levels of Ang II and increased levels of Ang-(1-7). These findings provide the first evidence demonstrating that estrogen may be protective against hypertension by shifting the vasoconstrictor-vasodilator balance of the RAS. Our hypothesis is that estrogen contributes to the regulation of arterial pressure augmenting the local regional vasodilator contributions of Ang-(1-7) and diminishing the vasoconstrictor actions of Ang II. A critical component of this effect of estrogen may arise through its down-regulation of angiotensin converting enzyme. We will determine the mechanism for these effects of estrogen by: 1) testing whether estrogen augments regional vasodilatory vascular reactivity to Ang-(1-7); (2) determining whether estrogen increases the affinity and number of the novel non-AT1/non-AT2 angiotensin receptor; 3) determining whether estrogen alters local angiotensin metabolism; and 4) testing whether estrogen reduces ACE mRNA through the classical estrogen-receptor, ERalpha, or the novel estrogen receptor, ERbeta. These novel studies will enhance our understanding of the role estrogen plays in promoting the paracrine production and participation of Ang-(1-7) in the regulation of regional vascular resistance, and may provide a new rationale for the use of estrogen to prevent and treat cardiovascular disease in postmenopausal women.