VASCULAR REACTIVITY--GENDER AND HORMONAL INFLUENCES

患心血管疾病风险的性别差异是 在更年期之前突出；然而，性别对 血管反应性和相关激素的性质不是 很好理解。使用Fischer 344大鼠模型，我们将在 体外血管对肾上腺素能神经刺激的反应性 松果体激素褪黑素与性腺血管分布 类固醇激素受体检验以下具体假设：1. 男性对肾上腺素能神经刺激更敏感 与女性相比，体外血管形成可以用一种 肾上腺素能神经功能的差异。我们将测量血管 去甲肾上腺素含量，刺激诱发的去甲肾上腺素释放，以及 共递质拮抗剂对三磷酸腺苷和神经肽Y的影响 肾上腺素能受体拮抗剂对肾上腺素能收缩反应的影响 神经刺激以确定性别和可能的阶段 发情周期影响血管的反应性。2.有一种关联性 褪黑素结合部位的存在与褪黑素对血管内皮细胞的影响 血管敏感性，两者均因性别、发情周期和 血管床。急性心血管疾病发病的昼夜节律变化 疾病、血管反应性和交感神经活动水平 描述得很好，昼夜节律荷尔蒙褪黑激素似乎影响 血管反应性。因此，我们将研究功能性反应 对褪黑素的血管系统，参与的血管的特异性 体温调节，血管褪黑素结合位点的分布，以及 随发情周期或性别的阶段而变化的。性腺类固醇 荷尔蒙对维持与性别有关的性别差异很重要 血管反应性，它们的影响可以与分布相关 血管系统中的激素受体。血管反应性 摘除卵巢的雌性和去势的雄性将与 而不需要激素替代。放射自显影将被用来定义 相关类固醇激素受体的血管分布。更好 对血管疾病性别差异基础的认识 反应性将为发病率和性别二型性提供新的线索 心血管疾病的特点。

Gender-related differences in risk for cardiovascular disease are prominent prior to the climacteric; however, the influence of gender on vascular reactivity and the nature of the hormones responsible are not well understood. Using the Fischer 344 rat model, we will measure in vitro vascular reactivity to adrenergic nerve stimulation and to the pineal hormone melatonin as well as the vascular distribution of gonadal steroid hormone receptors to test the following specific hypotheses: 1. Greater sensitivity to adrenergic nerve stimulation seen in male vasculature in vitro compared to female can be accounted for by a difference in adrenergic nerve function. We will measure vascular norepinephrine content, stimulation-evoked norepinephrine release, and the influence of antagonists of the co-transmitters ATP and neuropeptide Y and adrenergic receptor antagonists on contractile responses to adrenergic nerve stimulation to determine how gender and possibly stage of the estrous cycle influence vascular reactivity. 2. There is a correlation between presence of melatonin binding sites and effects of melatonin on vascular sensitivity, and both vary with gender, estrous cycle stage and vascular bed. Circadian variation in the onset of acute cardiovascular disease, vascular reactivity and levels of sympathetic activity has been well described, and the circadian hormone melatonin appears to influence vascular reactivity. Therefore we will investigate the functional response of the vasculature to melatonin, specificity for vessels involved in thermoregulation, distribution of vascular melatonin binding sites, and variation with stage of the estrous cycle or gender. 3. Gonadal steroid hormones are important in maintaining gender-related differences in vascular reactivity, and their effects can be correlated with distribution of hormone receptors in the vasculature. Vascular reactivity of ovariectomized females and castrated males will be studied with and without hormone replacement. Autoradiography will be used to define the vascular distribution of relevant steroid hormone receptors. Better understanding of the basis of gender-related differences in vascular reactivity will shed new light on the sexual dimorphism in incidence and characteristics of cardiovascular disease.