Aging Slows Vasoconstriction Dynamics in Skeletal Muscle Resistance Vessels

Abstract

With advancing age there is a reduced ability to tolerate orthostatic stress and perform exercise. An increase in peripheral vascular resistance (PVR) during both of these challenges, facilitated in part by sympathetically mediated vasoconstriction of resistance arteries, is requisite to maintain central venous return and arterial blood pressure. In aged subjects, the ability to rapidly enhance PVR during orthostatic challenges is diminished, which contributes to orthostatic intolerance in many aged individuals. The purpose of this preliminary investigation was to determine the rate of vasoconstriction to an alpha‐adrenergic agonist (i.e., sympathetic mimetic) in skeletal muscle arteries of young (6 mo old; n=4) and aged (24 mo old; n= 4) Fisher‐344 rats. Resistance arteries from the highly‐oxidative red portion of the gastrocnemius muscle were isolated and cannulated. Thereafter, the temporal characteristics of vasoconstriction [i.e., time‐delay (TD), rate of constriction, time to steady‐state (SS)] were quantified after exposure to 10−4M norepinephrine. With old age, the delay before the onset of constriction was ~ 5x longer than younger counterparts (young, 0.7 ± 0.1 vs. aged, 3.7 ± 0.4 s) and the time to SS was substantially prolonged with old age (young, 6.6 ± 0.4 vs. aged, 19.5 ± 1.2 s). Despite no difference in the overall magnitude of vasoconstriction between groups, the rate of vasoconstriction was blunted with old age (young, 35.9 ± 9.1 vs. aged, 14.1 ± 0.9 μm/s). With old age, there appears to be a severely diminished ability to rapidly vasoconstrict skeletal muscle resistance arteries. During orthostatic stresses, a reduced ability to vasoconstrict peripheral arteries would lead to blood pooling in the periphery and, subsequently, diminished venous return and an inability to maintain mean arterial pressure. The precise mechanisms responsible for the reduced rate of vasoconstriction (e.g., Ca2+ handling, altered vascular mechanical properties) are unknown and are currently being investigated. Whether the same deficits in vasoconstriction are present in arteries of other vascular beds (e.g., splanchnic region) remains to be determined.Support or Funding InformationNational Institutes of Health (AG25622), American Cancer Society (RSG‐14‐150‐01‐CCE)