Effects of Aging on Adipose Resistance Artery Vasoconstriction: Possible Implications for Orthostatic Blood Pressure Regulation

The purpose of this investigation was to determine mean arterial pressure (MAP) and regional vascular conductance responses in young and aged Fisher-344 rats during orthostatic stress, i.e., 70° head-up tilt (HUT). Both groups demonstrated directionally different changes in MAP during HUT (young, 7% increase; aged, 7% decrease). Vascular conductance during HUT in young rats decreased in most tissues but largely remained unchanged in the aged animals. Based on the higher vascular conductance of white adipose tissue from aged rats during HUT, resistance arteries from white visceral fat were isolated and studied in vitro. There was diminished maximal vasoconstriction to phenylephrine and norepinephrine (NE: young, 42 ± 5%; old, 18 ± 6%) in adipose resistance arteries from aged rats. These results demonstrate that aging reduces the ability to maintain MAP during orthostatic stress, and this is associated with a diminished vasoconstriction of adipose resistance arteries. With advancing age the ability to tolerate orthostatic stress (17, 22) and perform exercise (11, 15, 34) is reduced. One possible mechanism for these age-related changes is a diminished arterial vasoconstrictor responsiveness, which could impair redistribution of cardiac output during exercise and limit reductions in vascular conductance during orthostasis. The ability to diminish vascular conductance in nonactive tissue is requisite during orthostasis to maintain mean arterial pressure (MAP) and sustain adequate brain perfusion. However, whether regional vascular conductance during orthostasis is altered by aging remains unknown. Head-up tilt (HUT) has been utilized extensively to study cardiovascular system responsiveness to orthostatic stress in humans and animals (8, 13, 14, 16, 26, 31). Postural changes from the supine position to the upright posture elicit a blood volume shift from the thoracic cavity to the lower limbs (29), which results in reduced venous return and, subsequently, decreased stroke volume. The resultant decrease in cardiac output must be offset by a decrease in peripheral vascular conductance (PVC) to maintain arterial blood pressure (29). Since there is a greater incidence of orthostatic hypotension with advancing age (16, 25, 31, 38), the primary purpose of the present study was to determine whether a diminished ability to maintain MAP during an orthostatic stress is manifest in aged Fischer-344 rats and to identify whether alterations in regional vascular conductance correspond to a putative orthostatic hypotension. Specifically, we hypothesized that with HUT, aged animals will demonstrate a diminished vasoconstriction in some tissues, as evidenced by higher blood flows and vascular conductance relative to that in young adult rats. The results indicated an inability of old rats to diminish vascular conductance in several tissues, including white adipose tissue, during HUT. Therefore, a secondary purpose was to test the hypothesis that aging diminishes myogenic and adrenergic vasoconstriction of resistance vessels from white visceral adipose tissue. The results from this series of experiments may indicate an underlying mechanism for the old age-related orthostatic intolerance. Given that adipose tissue makes up a greater proportion of body composition with aging in rats (7) and humans (1), a reduced vasoconstriction of resistance vessels from this tissue could have significant ramifications on the ability to decrease peripheral vascular conductance during orthostatic challenges and with exercise among the elderly