MICROVASCULAR ADAPTATIONS IN HYPERTENSION

而高血压患者的主动脉和其他大动脉肥厚， 外周血管阻力通过小动脉的重塑而增加， 小动脉进入管腔较小的血管，与变化无关 在壁横截面积中。 这项研究计划的目标是 检验小动脉重塑由一个 平滑肌细胞和壁基质成分对慢性炎症的调节 使用三阶段方法进行血管收缩。 首先，扫描和 透射电子显微镜将用于确定静止长度 平滑肌细胞和内皮细胞占壁的百分比， 一肾一夹中的胶原、基底膜和平滑肌 （1 K1 C）高血压大鼠。 第二，假设慢性 血管收缩先于重塑将通过测量小动脉 lKlC大鼠脊髓背角肌张力和假设， 升高的压力是重塑的必要刺激，将在 主动脉缩窄的实验 第三，分子基础 肥大和重塑将使用原位杂交进行研究， 血管和小动脉中生长因子和基质蛋白的mRNA。 这 技术将首先应用于14天输注的模型， 降压剂量的血管紧张素II，因为它可能的作用，在肾 高血压及其对特定生长因子的影响 培养细胞的实验。 将探测主动脉和小动脉 bFGF、TGF-β、PDGF-A链、α-肌动蛋白、胶原蛋白和层粘连蛋白的mRNA。 图像分析将用于定量原位杂交信号。 假设平滑肌细胞的更新发生在 重建将通过免疫细胞化学检测增殖细胞 核抗原（细胞周期蛋白）。 这些技术将应用于船舶 从1 K1 C高血压大鼠。 结果将使结构的联系 定位于细胞类型的特异性基因表达的变化，即， 内皮细胞或平滑肌细胞。 结果比较 主动脉和小动脉可能表明为什么前者肥大，而 后期改造。 因此，这些研究将进一步阐明 从体外实验中提出的单个生长因子， 细胞类型之间的旁分泌关系形成了 高血压中的小动脉重塑和血管阻力增加。

While the aorta and other large arteries hypertrophy in hypertension, peripheral vascular resistance is increased by remodeling of arterioles and small arteries into vessels with smaller lumens, independently of changes in wall cross-sectional area. The goal of this research proposal is to test the overall hypothesis that arteriolar remodeling consists of an adjustment of smooth muscle cells and wall matrix components to chronic vasoconstriction using a three stage approach. First, scanning and transmission electron microscopy will be used to determine resting length of smooth muscle cells and percent of wall occupied by endothelium, collagen, basement membrane, and smooth muscle in one-kidney, one-clip (lKlC) hypertensive rats. Second, the hypothesis that chronic vasoconstriction precedes remodeling will be tested by measuring arteriolar tone in the spinotrapezius muscle of lKlC rats and the hypothesis that elevated pressure is a necessary stimulus for remodeling will be tested in experiments on aortic coarctation. Third, the molecular basis of hypertrophy and remodeling will be studied using in situ hybridization for mRNA of growth factors and matrix proteins in aortas and arterioles. This technique will be applied first to the model of 14-day infusion of subpressor doses of angiotensin II because of its possible role in renal hypertension and its effect on specific growth factors as suggested by experiments on cultured cells. Aortas and arterioles will be probed for mRNA for bFGF, TGF-beta, PDGF-A-chain, alpha-actin, collagen and laminin. Image analysis will be used to quantify the in situ hybridization signal. The hypothesis that turnover of smooth muscle cells occurs during remodeling will be tested by immunocytochemistry for proliferating cell nuclear antigen (cyclin). These techniques will then be applied to vessels from lKlC hypertensive rats. Results will allow the linkage of structural changes to specific gene expression localized to a cell type, i.e., endothelial cells or smooth muscle cells. Comparisons of results in the aorta and arterioles may indicate why the former hypertrophies while the latter remodels. Thus these studies will further delineate the role of individual growth factors suggested from in vitro experiments and reveal paracrine relationships between cell types that form the basis of arteriolar remodeling and increased vascular resistance in hypertension.