Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Abstract

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves by assessing 1) the age-related decline and 2) the effect of aerobic fitness. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in young (24 ± 1 yr) and older (64 ± 1 yr) endurance-trained and sedentary men (n = 7 per group) at baseline and during 35 min of local skin heating to 42°C at 1) untreated forearm sites, 2) forearm sites treated with bretylium tosylate (BT), which prevents neurotransmitter release from noradrenergic sympathetic nerves, and 3) forearm sites treated with yohimbine + propranolol (YP), which antagonizes α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC = SkBF/mean arterial pressure) and normalized to maximal CVC (%CVC(max)) achieved by skin heating to 44°C. Pharmacological agents were administered using microdialysis. In the young trained group, the rapid vasodilator response was reduced at BT and YP sites (P < 0.05); by contrast, in the young sedentary and older trained groups, YP had no effect (P > 0.05), but BT did (P > 0.05). Neither BT nor YP affected the rapid vasodilator response in the older sedentary group (P > 0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men and nonadrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system.

Body Temperature Regulation During Exercise and Hyperthermia in Diabetics

“…Black et al [92] used L-NAME (an NO synthase inhibitor) during acetylcholine infusions to block NO production and demonstrated that, in initially sedentary elderly individuals, increase in vascular responsiveness following 12 and 24 weeks of aerobic training was induced by the increase in action of NO in the skin. There are similar results in a longitudinal study [93] although a cross-sectional study reported no effects [94].…”

Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

“…The BT was administered via microdialysis at a concentration of 10 mM for 60 min at a rate of 4 μl min −1 (Hodges et al 2009b;Tew et al 2011b). The adequacy of the BT blockade was tested at the end of the experiment by 3 min of whole-body cooling, reducing T sk from 34 to 31…”

“…While it may seem counter-intuitive to assign a role for sympathetic nerves to cutaneous vasodilatation during skin heating, growing evidence exists in support of this assertion (Houghton et al 2006;Hodges et al 2008Hodges et al , 2009bTew et al 2011b). In this context, we sought to examine whether sympathetic nerves were involved in the augmented cutaneous vasodilator response to noxious skin heating.…”

“…Current data suggest that the initial peak and nadir of the vasodilator response are mediated by an axon reflex (Minson et al 2001;Tew et al 2011a). Additionally, the initial peak has been shown to have nitric oxide and noradrenergic sympathetic nerve components (Minson et al 2001;Houghton et al 2006;Hodges et al 2008Hodges et al , 2009bTew et al 2011b). Kellogg et al (1999) determined that the plateau phase of the cutaneous vasodilator response is ∼70% dependent on NO and have recently shown that the vasodilatation in response to local skin heating is produced by endothelial NO synthase (eNOS; Kellogg et al 2008Kellogg et al , 2009.…”

Assessment of Human Skin Microcirculation and Its Endothelial Function Using Laser Doppler Flowmetry

“…Apart from endothelial adaptations, changes in the sensitivity of vascular SMC to endothelial vasodilators or alterations in neural vascular control may play a role. By inducing local heating as a vasodilating stimulus, the study of Tew et al has shown that aerobic fitness affects the contribution of noradrenergic sympathetic fibers to the heating-induced LDF response (Tew et al, 2011). Indeed, it has been shown that endurance trained athletes have a diminished temperature threshold for active vasodilation i n s k i n c o m p a r e d t o m a t c h e d s e d e n t a r y controls (Fritzsche & Coyle, 2000).…”