Nonesterified Fatty Acids and Cardiovascular Aging

根据2003年NIA试点研究资助计划公告PAR-03-056（心血管和脑血管老化），提出了检查心血管自主控制的年龄相关变化与非酯化脂肪酸（NEFA）增加的关系。内脏肥胖的增加与NEFA水平直接相关，与迷走神经控制能力下降和交感神经活动增加有关。随着人类的衰老，自主控制也会发生类似的变化。随着年龄的增长，内脏肥胖和NEFA水平的增加可能导致心血管衰老的标志-压力反射敏感性降低，肌肉交感神经流出增加和血管硬化。然而，NEFA水平对自主神经功能的直接影响尚未得到很好的研究。因此，具体目的是确定NEFA升高是否与压力反射敏感性的年龄相关性降低、交感神经活性增加和血管僵硬度相关;并确定NEFA急性升高是否可以进一步降低健康老年人的压力反射敏感性、增加血管交感神经流出和血管僵硬度。逐搏动脉压变化、R-R间期和脉搏波速度的标准心血管测量将与直接交感神经记录和全身压力变化期间的同步超声衍生颈动脉图像相结合。这将同时评估心脏迷走神经和血管交感神经压力感受器反射增益，同时估计动脉压力转换到压力感觉区域的伸展。据推测，较低的压力反射控制，更大的交感神经流出和血管僵硬度与高NEFA水平，在那些低NEFA，压力反射控制可以急剧下降，交感神经活动和血管僵硬度都增加了短期的NEFA水平升高。将研究老年（55-70岁）正常和超重受试者，以提供广泛的循环NEFA水平，以检查NEFA与血管特征、功能和全身自主循环控制的关系。将评估急性NEFA升高对血管扩张性、压力反射敏感性和交感神经流出的影响。这项工作是临床相关的，因为这些协会可能会提供洞察心血管疾病的发病率随年龄增长的病因。

Examining the relation of age-related changes in cardiovascular autonomic control to increases in nonesterified fatty acids (NEFA) is proposed in response to 2003 NIA Pilot Research Grant program announcement PAR-03-056 (Cardiovascular and Cerebrovascular Aging). Increased visceral adiposity, which directly related to NEFA levels, is associated with decreased vagal control and increased sympathetic activity. Analogous changes in autonomic control occur with human aging. Increased visceral adiposity and NEFA levels with age could contribute to the hallmarks of cardiovascular aging - decreased baroreflex sensitivity, increased muscle sympathetic nervous outflow and vascular stiffening. However, direct effects of NEFA levels on autonomic function have not been well examined. Accordingly, the specific aims are to determine whether elevated NEFAs are associated with the age-related decrease in baroreflex sensitivity, increase in sympathetic nervous activity and vascular stiffness; and to determine whether acute elevations of NEFAs can further decrease baroreflex sensitivity, increase vascular sympathetic outflow and vessel stiffness in healthy older adults. Standard cardiovascular measures of beat-by-beat arterial pressure changes, R-R intervals and pulse wave velocity will be combined with direct sympathetic nerve recordings and concurrent ultrasound-derived carotid images during systemic pressure changes. This will assess cardiac vagal and vascular sympathetic baroreflex gain simultaneously while estimating arterial pressure transduction into stretch of a barosensory region. It is hypothesized that lower baroreflex control, greater sympathetic outflow and vascular stiffness are related to high NEFA level and that in those with low NEFAs, baroreflex control can be acutely decreased, sympathetic nervous activity and vessel stiffness both increased with short-term elevation of NEFAs. Older (55-70) normal and overweight subjects will be studied to provide a broad range of circulating NEFA levels to examine the relation of NEFAs to vascular character, function, and systemic autonomic circulatory control. Effects of acute NEFA elevation on vascular distensibility, baroreflex sensitivity, and sympathetic outflow will be assessed. This work is clinically relevant because these associations may provide insight into the etiology of the increased incidence of cardiovascular disease with age.