VASCULAR REACTIVITY--GENDER AND HORMONAL INFLUENCES

心血管疾病风险的性别相关差异 在更年期之前突出；然而，性别对 血管反应性和负责的激素的性质并不相同 很好理解。 使用 Fischer 344 大鼠模型，我们将测量 体外血管对肾上腺素能神经刺激和 松果体激素褪黑激素以及性腺的血管分布 类固醇激素受体来检验以下具体假设： 1. 男性对肾上腺素能神经刺激更敏感 与女性相比，体外血管系统可以通过以下因素来解释： 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 ATP 和神经肽 Y 拮抗剂的影响 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 动情周期影响血管反应性。 2.有相关性 褪黑激素结合位点的存在与褪黑激素的影响之间 血管敏感性，并且都随性别、动情周期阶段和 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，昼夜节律激素褪黑激素似乎会影响 血管反应性。因此我们将研究功能反应 脉管系统对褪黑激素的影响，涉及血管的特异性 体温调节、血管褪黑激素结合位点的分布，以及 随动情周期阶段或性别而变化。 3.性腺类固醇 激素对于维持性别相关差异很重要 血管反应性，其影响可以与分布相关 脉管系统中的激素受体。血管反应性 将研究切除卵巢的女性和阉割的男性 无需激素替代。放射自显影将用于定义 相关类固醇激素受体的血管分布。更好 了解血管性别相关差异的基础 反应性将为发病率和性别二态性提供新的线索 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.