VASCULAR KALLIKRIEN IN THE REGULATION OF VASCULAR TONE

血管激肽在血管张力调节中的作用

• 批准号: 5213427
• 负责人: A G SCICLI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5213427
• 关键词: ACE inhibitors; angiotensin /renin /aldosterone hypertension; angiotensin II; animal tissue; cardiovascular pharmacology; cell growth regulation; disease /disorder model; endothelin; fibrinolysis; hormone regulation /control mechanism; kallikreins; kinins; laboratory rat; messenger RNA; nitric oxide; plasminogen activator; polymerase chain reaction; prostaglandin endoperoxide synthase; renal hypertension; spontaneous hypertensive rat; tissue /cell culture; vascular endothelium; vascular resistance; vascular smooth muscle; vasoactive agent

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.

血管壁是重要的内分泌和旁分泌器官。 壁内释放或存在的生物活性物质调节 构成细胞的性质。 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。 激肽 释放内皮衍生因子，这是有效的血管扩张剂， 抑制血管平滑肌细胞（VSMC）的生长。 此外，本发明还提供了一种方法， 它们从内皮细胞释放组织纤溶酶原激活物（tPA）， 从而诱导纤维蛋白溶解。 我们的一般假设是， 激肽释放酶-激肽系统是血管壁的组成部分， 在功能上与血管内稳态有关。 我们推测 血管激肽释放酶释放激肽，其作用于或靠近血管的部位， 形成，有助于调节血管张力，纤维蛋白溶解和 增长 我们的具体目标是：目标一：1）阐明影响因素 调节激肽释放酶的含量和从动脉和静脉的释放; 2） 确定激肽是否从血管组织中释放; 3）鉴定 血管组织中的激酶。 目标二：1）确定是否 激肽刺激的tPA释放由EDRF的变化介导，和2） 确定施用后内源性激肽的增加是否 激肽酶抑制剂增加血浆纤维蛋白溶解活性。 目标四： 确定阻断激肽是否消除了部分抗增殖作用， 血管紧张素转换酶抑制剂（CEI）在球囊扩张术后的作用 内皮剥脱;目的V：确定血管是否 激肽释放酶-激肽系统在肾血管、体积依赖性和 遗传性高血压 我们将测量血管激肽释放酶含量， 2肾/1夹Goldblatt中的激肽释放酶mRNA和激肽释放酶释放 高血压、DOCA-盐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-激肽系统 有助于调节循环体内平衡。