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

Abstract

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.

Keywords: age; central venous pressure; cutaneous vasodilation; exercise; heat stress; tilt.

Fig. 1.

Cutaneous vascular conductance (%CVC_max) during supine passive heating in young (dash symbols) and older adults. The latter were tested after placebo (open symbols) and sapropterin administration (filled symbols). Data are shown at baseline and for each 0.1°C increase in esophageal temperature (T_es) throughout passive whole body heating. The increase in skin blood flow was blunted in older adults during placebo but was fully restored by sapropterin treatment. *P < 0.05, older placebo vs. young; †P < 0.05, older placebo vs. older sapropterin.

Fig. 2.

Cutaneous vascular conductance (%CVC_max; A) and cardiac output (B) in young (dash symbols) and older adults (placebo, open symbols; sapropterin, filled symbols). The experimental phases are presented in the order in which the protocol was conducted (upright thermoneutral, supine thermoneutral, supine passive heating, upright posture while heating was sustained, and upright and supine exercise while heating was sustained). Supine passive whole body heating is indicated by the gray box, with data points shown at ΔT_es = 0.4 and 0.8°C. *P < 0.05, older placebo vs. young; †P < 0.05, older placebo vs. older sapropterin.

Fig. 3.

The change (represented by the solid arrow between data points) in the relation between SkBF and cardiac output for young (dash symbols) and older adults (placebo, open symbols; sapropterin, filled symbols) depicted for each transition between experimental conditions. A: transition from supine thermoneutral to supine heating to ΔT_es = 0.8°C; B: transition from supine to upright posture while maintaining ΔT_es at 0.8°C; C: transition from upright rest to upright dynamic exercise while maintaining ΔT_es at 0.8°C. See text for further description.

Fig. 4.

Heart rate (A), stroke volume (B), and mean arterial pressure (MAP; C) in young (dash symbols) and older adults (placebo, open symbols; sapropterin, filled symbols). The experimental conditions are presented in the order in which the protocol was conducted (upright thermoneutral, supine thermoneutral, supine heated, upright heated, upright exercise, and supine exercise). Supine passive heating is indicated by the gray box, with data points shown at ΔT_es = 0.4 and 0.8°C. *P < 0.05, older placebo vs. young.