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.
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