VASCULAR KALLIKRIEN IN THE REGULATION OF VASCULAR TONE

血管壁是重要的内分泌和旁分泌器官。 在壁内释放或存在的生物活性物质调节 组成单元格的属性。腺激肽释放酶(一种激肽- 生成酶)及其mRNA存在于动脉和静脉中。激动素 释放内皮衍生因子，这些因子是有效的血管扩张剂和 抑制血管平滑肌细胞的生长。此外, 它们从内皮细胞释放组织纤溶酶原激活物(TPA)，并 从而诱导纤溶作用。我们的总体假设是 激肽释放酶-激肽系统是血管壁的重要组成部分， 在功能上参与了血管内稳态。我们假定 血管激肽释放酶释放激动素，这些激动素作用于其部位或附近。 形成，有助于调节血管张力，纤溶和 成长。我们的具体目标是：目标一：1)阐明影响因素 调节血管激肽释放酶的含量和释放；2) 确定激动素是否从血管组织中释放；3)识别 激氨酶存在于血管组织中。目标二：1)确定是否 激动素刺激的tPA释放是由EDRF的变化介导的，2)到 确定给药后内源性激肽是否增加 激氨酶抑制剂可增加血浆纤溶活性。目标四： 确定阻断激动素是否会取消部分抗增殖剂 血管紧张素转换酶抑制剂对球囊术后血管紧张素转换酶的影响 内皮剥脱；目的V：确定血管是否 激肽释放酶-激动素系统在肾血管疾病中的改变，呈容量依赖和 遗传性高血压。我们将测量血管激肽释放酶的含量， 2肾/1-夹Goldblatt激肽释放酶基因和激肽释放酶的研究 高血压、DOCA-SALT大鼠以及高血压前期和高血压SHR。 这些研究将确定血管激肽释放酶-激动素系统 有助于调节循环内稳态。

The vascular wall is an important endocrine and paracrine organ. Biologically active substances released or present within the wall modulate the properties of the constituent cells. Glandular kallikrein (a kinin- generating enzyme) and its mRNA are present in arteries and veins. Kinins release endothelium-derived factors, which are potent vasodilators and inhibit the growth of vascular smooth muscle cells (VSMC). In addition, they release tissue plasminogen activator (tPA) from endothelial cells and thereby induce fibrinolysis. Our general hypothesis is that the kallikrein-kinin system is an integral component of the vascular wall and is functionally involved in vascular homeostasis. We postulate that vascular kallikrein releases kinins which act at or near their site of formation, contributing to regulation of vascular tone, fibrinolysis and growth. Our specific aims are: Aim I: 1) To elucidate the factors regulating kallikrein content and release from arteries and veins; 2) To determine whether kinins are released from vascular tissue; 3) To identify the kininases present in vascular tissue. Aim II: 1) To determine whether kinin-stimulated release of tPA is mediated by changes in EDRF, and 2) to determine whether increasing endogenous kinins after administration of kininase inhibitors increases plasma fibrinolytic activity. Aim IV: To determine whether blocking kinins abolishes part of the antiproliferative effect of angiotensin-converting enzyme inhibitors (CEI) following balloon endothelial denudation; Aim V: To determine whether the vascular kallikrein-kinin system is altered in renovascular, volume-dependent and genetic hypertension. We will measure vascular kallikrein content, kallikrein mRNA and kallikrein release in 2 kidney/1-clip Goldblatt hypertension, DOCA-salt rats and both prehypertensive and hypertensive SHR. These studies will determine whether the vascular kallikrein-kinin system contributes to the regulation of circulatory homeostasis.