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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。大多数慢性肾脏疾病(CKD)患者都有高血压，是心血管疾病的高危人群。高血压的部分原因是血管中α1-肾上腺素能受体系统的高活性导致血管变窄。另一方面，身体产生的一氧化氮(NO)与α1-肾上腺素能受体系统相反。一氧化氮可以扩张血管，防止高血压。我们推测，CKD患者体内NO的低可获得性可能与α1-肾上腺素能受体系统的高活性有关。该方案是一项在健康受试者中进行的先导性研究，以指导我们在CKD患者中进行未来的研究。在健康人中，这项先导研究的具体目的是：1)确定α1肾上腺素能受体血管反应性是否可重复性；2)用NO钳技术测定α1肾上腺素能受体血管反应性。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。在筛查访问以确认合格后，受试者将在第二天通宵进入综合临床研究中心进行大约8小时的研究。我们将通过导管将不同数量的苯肾上腺素注入动脉来收缩前臂血管。我们将在给予苯肾上腺素的同时，使用维纳斯体积描记仪(一种类似于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，将阻断血管中一氧化氮的研究药物L-NMMA滴入同一动脉，然后将另一种药物硝普钠滴入同一动脉，硝普钠回馈一氧化氮，以恢复正常的前臂血流。这一过程被称为NO钳制技术，用于测量NO的影响。再次重复苯肾上腺素浓度和体积描记，以比较NO钳夹前和期间的血管狭窄程度。这项研究将教我们如何在肾脏疾病患者中进行关于NO与α1-肾上腺素能受体系统关系的未来研究。

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.