Impairments in central cardiovascular function contribute to attenuated reflex vasodilation in aged skin

During supine passive heating, increases in skin blood flow (SkBF) and cardiac output (Qc) are both blunted in older adults. The aim here was to determine the effect of acutely correcting the peripheral vasodilatory capacity of aged skin on the integrated cardiovascular responses to passive heating. A secondary aim was to examine the SkBF-Qc relation during hyperthermia in the presence (upright posture) and absence (dynamic exercise) of challenges to central venous pressure. We hypothesized that greater increases in SkBF would be accompanied by greater increases in Qc. Eleven healthy older adults (69 ± 3 yr) underwent supine passive heating (0.8°C rise in core temperature; water-perfused suit) after ingesting sapropterin (BH4, a nitric oxide synthase cofactor; 10 mg/kg) or placebo (randomized double-blind crossover design). Twelve young (24 ± 1 yr) subjects served as a comparison group. SkBF (laser-Doppler flowmetry) and Qc (open-circuit acetylene wash-in) were measured during supine heating, heating + upright posture, and heating + dynamic exercise. Throughout supine and upright heating, sapropterin fully restored the SkBF response of older adults to that of young adults but Qc remained blunted. During heat + upright posture, SkBF failed to decrease in untreated older subjects. There were no age- or treatment-related differences in SkBF-Qc during dynamic exercise. The principal finding of this study was that the blunted Qc response to passive heat stress is directly related to age as opposed to the blunted peripheral vasodilatory capacity of aged skin. Furthermore, peripheral impairments to SkBF in the aged may contribute to inapposite responses during challenges to central venous pressure during hyperthermia.