SYMPATHETIC TROPHIC EFFECTS ON ARTERIAL SMOOTH MUSCLE

动脉平滑肌细胞过度生长导致管腔狭窄 (SMC)在动脉壁疾病的病理基础中起重要作用 包括高血压和动脉粥样硬化。动脉的发现 SMC可以产生自己的增长因素引发了关于 控制完整动脉中生长因子合成的信号和 这些信号与正常循环需求相耦合的方式 疾病。我们最近发现α1-肾上腺素能受体(α1-AR) 刺激增加血小板衍生生长因子A链(PDGF-A) 在大鼠主动脉中表达，发现PDGFα受体也是 在这艘船上表达。在这里提出的工作中，我们将探索 α1-AR对PDGF-A调节的假说预测 表达提供了一种连接慢性交感神经活动的机制 血浆儿茶酚胺升高对动脉长期营养变化的影响 SMC质量和壁厚。使用RNA印迹分析，核糖核酸酶保护 化验、免疫组织化学和原位杂交技术，我们将 部分成年大鼠PDGF-A和PDGFα受体的测定和定位 刺激α1-AR后的动脉。采用这样的方法 ，然后我们将检验我们的三个重要预测 假设：(1)我们将确定直流电刺激是否 供应动脉壁的交感神经本身可增加PDGF-A 表情。(2)我们将检查幼年大鼠的部分动脉 当神经肌肉的营养作用最明显时，问：做这些 血管也表现出PDGF-A和/或PDGFα的α1-AR刺激。 受体表达？响应单元格位于 血管壁？是否还有其他已知的生长因子可以改变PDGF-A的作用 受α1-Ars调控？(3)我们将使用PDGF中和抗体- AA in试图证明这种生长因子在SMC中的功能作用 体外对α1-AR刺激的生长反应。我们之前的发现 α1-AR刺激增加主动脉PDGF-A的表达 关于α1-AR在SMC生长中作用的重要新问题 控制，并强调有必要更多地了解内源性 旁分泌生长因子的产生与循环的耦合机制 动脉壁内的需求。

Lumenal narrowing due to excessive growth of arterial smooth muscle cells (SMC) plays a critical role in the pathologic basis of artery wall diseases including hypertension and atherosclerosis. The discovery that arterial SMC can produce their own growth factors raises new questions about the signals that control growth factor synthesis in intact arteries and the ways that these signals are coupled to normal circulatory demands and disease. We recently showed that alpha1-adrenergic receptor (alpha1-AR) stimulation increased platelet-derived growth factor A-chain (PDGF-A) expression in rat aorta and found that the PDGF alpha-receptor is also expressed in this vessel. In the work proposed here, we will explore predictions of the hypothesis that alpha1-AR regulation of PDGF-A expression provides a mechanism linking chronic sympathetic nerve activity and elevated plasma catecholamines to long-term trophic changes in arterial SMC mass and wall thickness. Using RNA blot analysis, RNase protection assays, immunohistochemistry, and in situ hybridization techniques, we will measure and localize PDGF-A and PDGF alpha-receptor in selected adult rat arteries after alpha1-AR stimulation. Employing the methods thus established, we will then examine three important predictions of our hypothesis: (1) We will determine if direct electrical stimulation of sympathetic nerves supplying the artery wall can itself increase PDGF-A expression. (2) We will examine selected arteries from young rats at ages when nerve-muscle trophic effects are most pronounced and ask: Do these vessels also show alpha1-AR-stimulation of PDGF-A and/or PDGF alpha- receptor expression? Where are the responding cells localized within the vessel wall? Are other growth factors known to modify PDGF-A action also regulated by alpha1-ARs? (3) We will use neutralizing antibodies to PDGF- AA in attempts to show a functional role for this growth factor in SMC growth responses to alpha1-AR stimulation in vitro. Our previous finding that alpha1-AR stimulation increases aortic PDGF-A expression raises important new questions about the role of the alpha1-AR in SMC growth control and emphasizes a need to know more about the nature of endogenous mechanisms that couple paracrine growth factor production to circulatory demands within the artery wall.