PILOT STUDY ON THE ROLE OF NITRIC OXIDE IN A1 ADRENERGIC VASOREACTIVITY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大多数慢性肾脏病（CKD）患者都有高血压，并处于心血管疾病的高风险之中。高血压可以部分地由血管中的α 1-肾上腺素受体系统的高活性导致的血管狭窄引起。另一方面，由身体产生的一氧化氮（NO）对抗α 1-肾上腺素受体系统。一氧化氮能扩张血管，防止高血压。我们推测，低可用性的NO可能是负责高活性的α 1-肾上腺素受体系统在CKD患者。本方案是一项在健康受试者中进行的初步研究，旨在指导我们在CKD患者中进行未来的研究。 在健康人群中进行的初步研究的具体目的是：1）确定α 1-肾上腺素受体血管反应性是否可重现; 2）用NO钳夹技术确定α 1-肾上腺素受体血管反应性。为了实现这些具体目标，我们将同意并招募8名血压正常的健康人。在确认合格性的筛选访视后，受试者将在第二天入住综合临床研究中心过夜，进行约8小时的研究。 我们将通过导管向动脉内注入不同剂量的苯肾上腺素来收缩前臂血管。我们将在给予苯巴比妥的同时用静脉体积描记法（一种类似血压袖带的测量工具）测量受试者的血流量。我们将重复测试，看看是否得到相同的结果。 然后，一种研究药物，L-NMMA，阻止血管中的NO，将被滴入同一动脉，然后是另一种药物硝普钠，提供NO，以恢复正常的前臂血流。该程序被称为NO钳夹技术，用于测量NO的作用。将再次重复苯肾上腺素浓度和体积描记术，以比较NO钳夹之前和期间的血管狭窄。这项研究将教会我们如何在肾脏疾病患者中进行NO与α 1-肾上腺素受体系统之间关系的未来研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most patients with chronic kidney disease (CKD) have high blood pressure and are at high risk for cardiovascular disease. High blood pressure can be partly caused by narrowing of blood vessels from high activity of the alpha1-adrenoceptor system in blood vessels. On the other hand, nitric oxide (NO), produced by the body, opposes the alpha1-adrenoceptor system. NO widens blood vessels and prevents high blood pressure. We hypothesize that low availability of NO may be responsible for high activity of alpha 1-adrenoceptor system in patients with CKD. This protocol is a pilot study in healthy subjects to guide us in performing future studies in patients with CKD. The specific aims of the pilot study, in healthy people, are to 1) determine whether alpha 1-adrenoceptor vasoreactivity is reproducible and 2) determine alpha 1-adrenoceptor vasoreactivity with the NO clamp technique. To carry out these specific aims, we will consent and enroll eight healthy people with normal blood pressure. After a screening visit to confirm eligibility, subjects will be admitted to the General Clinical Research Center overnight for an approximately 8 hour study the following day. We will constrict the forearm blood vessels by giving different amounts of phenylephrine into the artery through a catheter. We will measure the subjects blood flow with venus plethysmography ( a measuring tool like a blood pressure cuff) while giving the phenylephrine. We will repeat the tests to see if we get the same results. Then, a research medication, L-NMMA, which blocks NO in the blood vessel, will be dripped into the same artery followed by another medication nitroprusside, which gives back NO, to restore normal forearm blood flow. This procedure is called the NO clamp technique and is used to measure the effects of NO. The phenylephrine concentrations and plethysmography will be repeated again to compare vessel narrowing before and during the NO clamp. This research will teach us how to perform future studies on the relationship between NO and the alpha 1-adrenoceptor system in patients with kidney disease.