ALPHA-ADRENERGIC REACTIVITY IN HUMAN HYPERTENSION

人类高血压中的α-肾上腺素能反应

基本信息

批准号：
3081776
负责人：
BRENT M EGAN
金额：
$ 6.26万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1989-06-30
项目状态：
已结题

项目摘要

The pathophysiologic hallmark of essential hypertension is an elevated peripheral vascular resistance. The mechanism of this resistance abnormality remains an enigma. Previous research has indicated that structural vascular abnormalities, increased alpha-receptor sensitivity and abnormalities in membrane transport of cations may explain the increased arterial resistances in patients with hypertension. Other research has indicated that these same factors participate in salt-sensitive hypertension. The ultimate objectives of this proposal, based on three related studies of the human forearm vasculature, are to 1) define the cause(s) in the hypertensive patient for an increased arterial reactivity to vasopressor agents, especially norepinephrine (NE), 2) identify the pathophysiologic mechanism conferring "salt-sensitivity" present in some hypertensive patients, 3) determine if the abnormalities found are specific for vascular tissue or present in the pupillary responses of the eye as well. Three criteria for evaluating vascular structure, one criterion of sympathetic forearm vascular tone, and one measure each of alpha-receptor sensitivity and affinity will be obtained by constructing complete dose of intraarterial NE to calculated forearm vascular resistance response in hypertensive and normotensive humans. Vascular structure will also be evaluated by minimum FAVR after 10' of ischemic forearm exercise, and the similarity of vascular reactivity to NE and angiotensin II. Forearm sympathetic tone will be evaluated by two methods: 1) vasodilator response to i.a. phentolamine and 2) the product of sympathetic drive (plasma catecholamines) and forearm alpha-receptor sensitivity (l/dose of i.a. NE which increases FAVR by 50%). Membrane transport of cations will be evaluated by in vitro assay of erythrocyte Na+/K+ fluxes. The mechanism of salt-sensitivity in hypertension will be investigated by performing the previous studies on hypertensive and normotensive subjects during both high-salt (250 mEq/d) and low-salt (20 mEq/d) balance. The presence of abnormal reactivity in nonvascular tissue will be investigated by pupillometric assessment of the light reflex, pupil size in the dark and mydriatic sensitivity to phenylephrine.

基本高血压的病理生理标志是升高周围血管阻力。这种抵抗的机制异常仍然是一个谜。以前的研究表明结构性血管异常，α受体灵敏度提高和阳离子膜运输的异常可能解释了增加高血压患者的动脉抗性。其他研究也有表明这些相同的因素参与盐敏感高血压。该提案的最终目标，基于三个人类前臂脉管系统的相关研究是1）定义高血压患者的原因提高了动脉反应性致血管加压剂，尤其是去甲肾上腺素（NE），2）确定在某些中赋予“盐敏感性”的病理生理机制高血压患者，3）确定发现的异常是否特定对于血管组织或眼睛的瞳孔反应中的存在出色地。评估血管结构的三个标准，一个标准交感的前臂血管张力，每一个测量α受体敏感性和亲和力将通过构建完整的剂量来获得核内NE到计算的前臂血管抗性反应高血压和正常的人类。血管结构也将是在缺血性前臂运动10'后，通过最小favr评估，血管反应性与NE和血管紧张素II的相似性。前臂同情语气将通过两种方法评估：1）血管扩张器响应到I.A.苯丙胺和2）交感神经驱动的乘积（等离子体儿茶酚胺）和前臂α受体灵敏度（I.A. NE的L/剂量这将FAVR增加了50％）。阳离子的膜运输将是通过体外测定红细胞Na+/K+通量评估。机制高血压中的盐敏感性将通过执行先前关于两者期间高血压和正常受试者的研究高盐（250 meq/d）和低盐（20 meq/d）平衡。存在非血管组织反应性异常将通过对光反射，瞳孔大小在黑暗和对苯肾上腺素的麦乳干敏感性。