AGING, ANTIHYPERTENSIVE THERAPY, AND BLOOD PRESSURE REGULATION

衰老和高血压都会损害血压调节，使高血压老年人容易发生低血压。高血压还可能损害大脑的自动调节，使高血压老年人在降低血压的压力下容易晕厥和福尔斯。在之前的资助期间，我们发现i）老年受试者的BP升高与直立性（OH）和餐后（PPH）低血压独立相关，ii）成功治疗高血压的老年疗养院居民的OH患病率低于未控制的高血压患者，iii）钙通道阻滞剂尼卡地平降低BP可改善PPH。针对这些发现，我们假设血压升高损害了老年人的大脑和全身血压调节，并且成功治疗高血压可能会改善对过度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是很重要的，因为许多医生不愿意治疗老年人的高血压，因为他们害怕引起低血压和晕厥。研究将包括两个部分; i）对老年血压正常（N=50）、控制的高血压（N = 50）、控制的高血压（N =50）和未控制的高血压（N=70）受试者进行横断面组间比较（>65岁），以确定高血压对脑自动调节和全身血压调节的影响，和ii）一项前瞻性研究，对未控制的高血压进行为期6个月的药物降压，以确定其对脑自动调节的影响（在Valsalva动作和头高位倾斜期间使用经颅多普勒超声），压力反射功能（Valsalva的IV期）、颈动脉的搏动扩张性、多普勒颈动脉图像和BP的逐搏记录）和心血管对直立性的适应（通过CO2再呼吸和脉搏轮廓分析的心输出量和通过静脉闭塞体积描记法的前臂血管收缩）。将使用多变量和重复测量方差分析对数据进行分析。如果这项研究的结果表明，明智的抗高血压治疗可以降低高血压老年人低血压、晕厥和脑缺血的风险，那么它可能会大大改善老年护理。

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.