AVIAN VASCULAR FUNCTION--INTERACTION WITH ANGIOTENSIN

禽类血管功能——与血管紧张素的相互作用

• 批准号: 2702260
• 负责人: HIROKO NISHIMURA
• 金额: $ 25.92万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2702260
• 关键词: Aves; alpha adrenergic receptor; angiotensins; animal age group; artery; atherosclerosis; biological signal transduction; blood pressure; cardiovascular function; catecholamines; cellular pathology; cyclic GMP; hemodynamics; nitric oxide; phenotype; vascular endothelium; vascular smooth muscle; vasodilators

DESCRIPTION: The overall aim of this proposal is to investigate the role of the VES unit in the control of vascular function, utilizing a unique interaction between ANG and the avian vascular cells. A long-term goal will be to elucidate the cellular and molecular mechanisms of the VES communication and to determine local humoral and hemodynamic factors that regulate the VES unit in normal and impaired blood vessels. The unique aspects of the avian vascular model include: 1) Birds have elevated blood pressure and plasma cateholamines and show both spontaneously developed and endothelium injury- induced vascular neointimal plaques. 2) Two types of vascular smooth muscle (VSM) cells appear to be present, one of which may be atherogenic. 3) ANG exerts endothelium-dependent vasorelaxation via endothelium-derived relaxing factor (EDRF)/cGMP and vasopressor action by releasing catecholamines; these actions are selectively inhibitable. 4) Prostacyclin synthase appears absent in fowl aortae. The applicant hypothesizes that endothelial dysfunction, due to damage caused by high perfusion pressure, and impaired VES communication may lead to, or aggravate, neointimal proliferative lesions in atherogenesis- prone vessels. The dual interaction of ANG with vascular cells in fowl will provide a useful tool for studying the role of the VES unit in the regulation of normal and impaired vascular function. Aim one is to characterize age- (or blood pressure-) related phenotype changes of the VES unit of fowl aortae focusing on: 1) endothelial function (endothelium-dependent relaxation and permeability) and cellular signals (cGMP/nitric oxide) and 2) VSM function (contraction and growth promotion) and calcium signalling and their relationship to blood pressure and neointimal proliferative plaques. Four age-groups will be used, representing those preceding and following establishment of vascular lesions and blood pressure. Furthermore, morphological and physiological properties will be compared between naturally developed and endothelium injury-induced neointimal plaque cells. Aim two is to determine whether stimulation of endothelial function by ANG or inhibition of alpha-adrenergic receptors helps maintain normal VES unit function and prevents development of vascular plaques and whether, in contrast, endothelial impairment (by EDRF/nitric oxide synthase inhibition or endothelium injury) or increased catecholamines accelerate VES unit dysfunction and neointimal hyperplasia, possibly leading to elevation of blood pressure. ANG and inhibitors will be infused by osmotic minipump, and the morphology and function of the VES unit will be examined as above. ANG interaction with the vascular system in fowl will provide an unique model for studying the role and cellular mechanism of the VES unit in the control of normal and impaired vascular function.

描述：本提案的总体目标是调查 VES装置在控制血管功能中的作用， ANG与禽类血管细胞之间的相互作用。 一个长期目标 将阐明VES的细胞和分子机制 沟通，并确定当地的体液和血液动力学因素 调节正常和受损血管中的VES单位。 的 鸟类血管模型的独特方面包括：1）鸟类具有 血压和血浆胆碱胺升高，并显示两者 自发性和内皮损伤诱导的血管 新生内膜斑块 2)两种类型的血管平滑肌（VSM）细胞 似乎存在，其中之一可能是动脉粥样硬化。 3)ANG发挥 内皮依赖性血管舒张 因子（EDRF）/cGMP和通过释放儿茶酚胺的血管加压作用; 这些动作是可选择性地重复的。 4)前列环素合成酶 出现在家禽中。 申请人假设， 内皮功能障碍，由于高灌注引起的损伤 压力和VES通信受损可能导致或加重， 易发生动脉粥样硬化血管的新生内膜增生性病变。 的 ANG与家禽血管细胞的双重相互作用将提供 有用的工具，研究的作用，VES单位在调节 正常和受损的血管功能。 目的一是描述年龄特征- (or与血压相关的鸡VES单位表型变化 重点关注：1）内皮功能（内皮依赖性 松弛和渗透性）和细胞信号（cGMP/一氧化氮） 2）VSM功能（收缩和生长促进）和钙 信号传导及其与血压和新生内膜的关系 增殖性斑块 将使用四个年龄组，代表这些 在建立血管病变和血液 压力 此外，形态和生理特性将 比较自然发育和内皮损伤诱导 新生内膜斑块细胞。 目的二是确定刺激是否 通过ANG或抑制α-肾上腺素能 受体有助于维持正常的VES单位功能， 血管斑块的发展，与此相反， 损伤（通过EDRF/一氧化氮合酶抑制或内皮 损伤）或增加的儿茶酚胺加速VES单位功能障碍， 新生内膜增生，可能导致血压升高。 ANG和抑制剂将通过渗透微泵输注， 将如上检查VES单元的形态和功能。 ANG 与家禽血管系统的相互作用将提供独特的 研究VES单位的作用和细胞机制的模型 控制正常和受损的血管功能。