RECEPTOR SIGNALING IN POLYPLOID VASCULAR SMOOTH MUSCLE

多倍体血管平滑肌中的受体信号传导

• 批准号: 3358740
• 负责人: TOMMY A BROCK
• 金额: $ 9.04万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358740
• 关键词: acidity /alkalinity; angiotensin II; calcium metabolism; cardiovascular pharmacology; cell cell interaction; cytogenetics; diploidy; flow cytometry; fluorescence microscopy; gene expression; hypertension; laboratory rat; membrane potentials; muscle cells; platelet derived growth factor; polyploidy; potassium chloride; receptor sensitivity; spontaneous hypertensive rat; tissue /cell culture; vascular smooth muscle

The proposed research program focuses on ionic, biochemical and cellular mechanisms of vasoconstrictor agonist (angiotensin II, KC1) and growth factor (platelet-derived growth factor) action on diploid and polyploid vascular smooth muscle cells (VSMC) isolated from different blood vessels (aorta, caudal artery and mesenteric artery) of normotensive, spontaneously hypertensive and DOCA/salt hypertensive rats. Freshly isolated, as well as cultured VSMC will be used in these studies. A detailed analysis of cytosolic calcium and pH will be made using flow cytometry and newly developed multiparameter analytical methods related to fluorescence-ratio imaging microscopy. The specific aims include: 1) providing a detailed cell-by-cell analysis of resting cytosolic calcium and pH, as well as membrane potential, in diploid/tetraploid VSMC via flow cytometry. In addition, differences in the spatial and regional distribution (nuclear vs. cytosolic) of cellular calcium and pH will be assessed; 2) determining whether diploid/polyploid (tetraploid, octaploid) VSMC from hypertensive animals possess altered signal transduction pathways as compared to normal diploid VSMC. We will also compare and contrast the regional differences in cytosolic calcium and pH following angiotensin II and PDGF stimulation; 3) evaluating the physiological relevance of cell-cell interactions between diploid and polyploid populations of VSMC; and 4) examining the cytogenetic mechanisms which contribute to the development of the polyploid VSMC phenotype. These studies should contribute to our basic understanding of the mechanisms of normal and altered VSMC responsiveness related to the pathogenesis of hypertension, atherosclerosis and arterial vasospasm.

提出的研究计划侧重于离子，生化和