AGING, ANTIHYPERTENSIVE THERAPY, AND BLOOD PRESSURE REGULATION

衰老和高血压都会损害血压调节，使老年高血压患者容易发生低血压。高血压还可能损害大脑的自动调节，使高血压老年人容易晕厥，并在降低血压的压力下摔倒。在以前的资助期间，我们发现：i)老年受试者的血压升高与立位(OH)和餐后低血压(PPH)独立相关；ii)成功治疗高血压的老年疗养院居民的OH患病率低于那些未受控制的高血压患者；以及iii)钙通道阻滞剂尼卡地平降低血压可以改善PPH。作为对这些发现的回应，我们假设血压升高损害了老年人的大脑和全身血压调节，成功治疗高血压可能会改善对低血压应激的适应性大脑和全身调节反应。对这一假设的严格检验很重要，因为许多医生不愿治疗老年人的高血压，因为他们担心引发低血压和晕厥。这项研究将由两部分组成：i)老年正常血压(N=50)、控制高血压(N=50)、控制高血压(N=50)和未控制高血压(N=70)受试者的横断面组间比较(&GT；I)一项前瞻性研究，以确定高血压对脑自动调节和全身血压调节的影响；ii)一项未控制的高血压前瞻性研究，以确定持续6个月的药物降压对脑自动调节的影响(使用Valsalva动作和仰卧位时的经颅多普勒超声)、压力反射功能(Valsalva第四期)、颈动脉的搏动性扩张性、每搏颈动脉图像和血压的每搏记录(通过二氧化碳再呼吸和脉搏轮廓分析测定心输出量，以及通过静脉阻塞法测定前臂血管收缩)和心血管适应(通过二氧化碳再呼吸和脉搏轮廓分析测定的心输出量，以及通过静脉阻塞术引起的前臂血管收缩)。数据将使用多变量和重复测量的方差分析进行分析。这项研究的结果可能会极大地改善老年护理，如果他们表明明智的抗高血压治疗降低了高血压老年人低血压、晕厥和脑缺血的风险。

Both aging and hypertension impair BP regulation, predisposing hypertensive elderly people to hypotension. Hypertension may also impair cerebral auto- regulation, making hypertensive elderly vulnerable to syncope and falls during stresses that reduce BP. During previous funding periods, we showed that i) BP elevation in elderly subjects is independently associated with orthostatic (OH) and postprandial (PPH) hypotension, ii) elderly nursing home residents successfully treated for hypertension have a lower prevalence of OH than those with uncontrolled hypertension, and iii) BP lowering with the calcium channel blocker nicardipine ameliorates PPH. In response to these findings we hypothesize the BP elevation impairs cerebral and systemic BP regulation in the elderly, and that the successful treatment of hypertension may improve adaptive cerebral and systemic regulatory responses to hypotensive stress. Rigorous testing of this hypothesis is important because many physicians are reluctant to treat hypertension in the elderly for fear of precipitating hypotension and syncope. The study will consist of 2 parts; i) a cross-sectional, between-group comparison of elderly normontensive (N=50), controlled hypertensive (N=50), controlled hypertensive (N=50), and uncontrolled hypertensive (N=70) subjects (>65 years), to determine the effects of hypertension on cerebral auto-regulation and systemic BP regulation, and ii) a prospective study of uncontrolled hypertensive to determine the effect of pharmacologic BP lowering for 6 months, on cerebral auto-regulation (using transcranial Doppler ultrasound during the Valsalva maneuver and head-up tilt), baroreflex function (phase IV of the Valsalva), pulsatile distensibility of the carotid artery, beat-to-beat recordings of Doppler carotid images and BP), and cardiovascular adaptation to orthostasis (cardiac output by CO2 rebreathing and pulse contour analysis, and forearm vasoconstriction by venous occlusion plethysmography). Data will be analyzed using multi-variate and repeated measures analyses of variance. The results of this study may greatly improve geriatric care if they show that judicious anti-hypertensive therapy reduces the risk of hypotension, syncope, and cerebral ischemia in hypertensive elders.