This FIRST award will investigate the relation of decreased cardiovascular function to increased vascular stiffness with age and is responsive to a 1995 National Institute on Aging program announcement (PA-95-074). Age-related stiffening of carotid barosensory areas would effectively desensitize the baroreflex since baroreceptors are responsive to pressure-related stretch. The arterial baroreflex is a key determinant of the mean level of both vagal and sympathetic outflows; thus, the lower vagal and greater sympathetic outflows associated with cardiovascular diseases may result from blunted baroreflexes due to increased vascular stiffness. Though arterial stiffness increases with age, it is negatively related to aerobic capacity regardless of age. Thus, chronic aerobic training may help to maintain baroreflex autonomic circulatory control by mitigating age-related arterial stiffening.
The specific aims of this proposal are to determine if: 1) age-related decreases in baroreflex control of vagal and sympathetic outflows are related to greater carotid stiffness, 2) age-related declines in baroreflex control of vagal and sympathetic outflows are reduced by lesser carotid stiffness associated with aerobic fitness, and 3) a program of regular aerobic exercise training in older humans increases baroreflex control of vagal and sympathetic outflows due to decreased carotid stiffness. It is hypothesized that the age-related reductions in baroreflex circulatory control associated with increased carotid stiffness and altered basal autonomic outflow can be reversed by exercise training. To fulfill these aims, state-of-the-art neurophysiologic and ultrasonographic measures will be made to assess baroreflex gain of autonomic outflow relative to the true stimulus for baroreceptor activation changes in carotid dimensions. Young (20-30 yr.) and older (60-80 yr.) men and women will be rigorously screened to determine the influence of the aging process per se (as opposed to disease, inactivity, etc.) on baroreflex function, basal autonomic outflow, and carotid stiffness. The possible reversal of age-related declines by aerobic exercise training will be assessed both cross-sectionally and longitudinally. The investigator indicates that these studies are unique; that there are no data which relate changes in barosensory dimensions to concurrent changes in cardiovascular autonomic outflow in humans. He feels that despite data indicating that carotid stiffness plays a significant role in baroreflex function, it is unknown if increased stiffness in barosensory areas results in the age-related reduction in baroreflex gain, ultimately decreasing vagal and increasing sympathetic outflow. Further, he feels that it is unknown if aerobic fitness modulates these age-related effects. He states that this information is crucial to understand if blunted baroreflex function secondary to vascular stiffening is the conduit by which aging compromises autonomic circulatory control and increases cardiovascular morbidity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG014376-03
Application #
6016816
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Program Officer
Dutta, Chhanda
Project Start
1997-06-01
Project End
2002-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Hebrew Rehabilitation Center for Aged
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02131
Callegaro, Carine C; Taylor, J Andrew (2012) Age-related effects of vagotonic atropine on cardiovagal baroreflex gain. Neurobiol Aging 33:368-74
Ler, A S H; Cohen, M A; Taylor, J A (2010) A planar elliptical model of cardio-vagal hysteresis. Physiol Meas 31:857-73
Tan, Can Ozan; Taylor, J Andrew (2010) Does respiratory sinus arrhythmia serve a buffering role for diastolic pressure fluctuations? Am J Physiol Heart Circ Physiol 298:H1492-8
Picard, Glen; Tan, Can Ozan; Zafonte, Ross et al. (2009) Incongruous changes in heart period and heart rate variability with vagotonic atropine: implications for rehabilitation medicine. PM R 1:820-6
Studinger, Péter; Goldstein, Richard; Taylor, J Andrew (2009) Age- and fitness-related alterations in vascular sympathetic control. J Physiol 587:2049-57
Tan, Can Ozan; Cohen, Michael A; Eckberg, Dwain L et al. (2009) Fractal properties of human heart period variability: physiological and methodological implications. J Physiol 587:3929-41
Deley, Gaelle; Picard, Glen; Taylor, J Andrew (2009) Arterial baroreflex control of cardiac vagal outflow in older individuals can be enhanced by aerobic exercise training. Hypertension 53:826-32
Myers, Christopher W; Farquhar, William B; Forman, Daniel E et al. (2002) Carotid distensibility characterized via the isometric exercise pressor response. Am J Physiol Heart Circ Physiol 283:H2592-8
Hunt, B E; Farquhar, W B; Taylor, J A (2001) Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men? Circulation 103:2424-7
Hunt, B E; Fahy, L; Farquhar, W B et al. (2001) Quantification of mechanical and neural components of vagal baroreflex in humans. Hypertension 37:1362-8

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