This proposal arises from previous gerontologic research showing that healthy women have greater heart rate (HR) variability and lower blood pressure (BP) variability that healthy men across all ages, and that chronic estrogen replacement in postmenopausal women is associated with a reduction in the amplitude of beat-to-beat Mayer-wave BP oscillations after posture change or meal ingestion. These preliminary cross-sectional data suggest that estrogen may suppress vasomotor instability in healthy elderly women. The investigators now seek to determine prospectively estrogen's role and mechanism(s) in damping arterial pressure Mayer waves in response to sympathoexcitatory stimuli. They hypothesize that estrogen decrease BP oscillations after sympathetic activation, and that this effect is not due to changes in vascular sympathetic outflow or arterial baroreflex gain, but is secondary to reductions in vascular responsiveness to sympathetic activity associated with enhanced flow-mediated vasodilation. This hypothesis will be tested by measuring beat-to-beat BP, sympathetic nerve activity to the leg vasculature (SNA), and calf blood flow (CBF) in response to nitroprusside infusion, in 24 healthy post-menopausal women before and six months after estrogen replacement therapy or placebo, given in randomized fashion. Baroreflex control of vascular sympathetic outflow will be assessed by SNA responses to nitroprusside and phenylephrine, and sympathetic vasomotor transduction will be determined from the slope of the relation between sympathoexcitatory (SN) and vasoconstrictor (CBF) responses to isometric exercise. Flow-mediated vasodilation will be assessed during reactive hyperemia. They will examine the relationships between arterial pressure Mayer wave amplitude and vascular sympathetic outflow, baroreflex gain, sympathetic vasomotor transduction, and flow-mediated vasodilation before and after estrogen and placebo treatment. The results will elucidate the physiologic consequences of estrogen loss in vascular tissue, and may suggest a therapeutic role for estrogen in elderly women with impaired autonomic control of BP.
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