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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。大多数慢性肾脏疾病（CKD）患者都有高血压，并且有患心血管疾病的高风险。高血压的部分原因是由于血管中α - 1肾上腺素受体系统的高活性导致血管变窄。另一方面，一氧化氮（NO），由身体产生，对抗α - 1肾上腺素受体系统。一氧化氮可以扩张血管，预防高血压。我们推测一氧化氮的低可利用性可能是CKD患者α 1-肾上腺素能受体系统高活性的原因。该方案是一项健康受试者的试点研究，以指导我们在CKD患者中进行未来的研究。在健康人群中进行试点研究的具体目的是：1)确定α 1-肾上腺素能受体血管反应性是否可重复；2)用NO钳技术确定α 1-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。在确认资格的筛选访问后，受试者将在第二天进入普通临床研究中心过夜，进行大约8小时的研究。我们将通过导管将不同量的苯肾上腺素注入动脉来收缩前臂血管。我们将在给病人注射苯肾上腺素的同时用血管容积描记仪（一种类似于血压袖带的测量工具）测量病人的血流。我们将重复测试，看看是否能得到相同的结果。然后，将阻断血管NO的研究药物L-NMMA滴入同一条动脉，然后将另一种药物硝普赛滴入同一条动脉，硝普赛会释放NO，以恢复正常的前臂血流。这个过程被称为NO夹紧技术，用于测量NO的影响。将再次重复苯肾上腺素浓度和体积脉搏图，以比较NO钳夹前后的血管狭窄。这项研究将指导我们如何在肾脏疾病患者中开展NO与α 1-肾上腺素能受体系统之间关系的进一步研究。

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.