Neurally mediated vasoconstriction is capable of decreasing skin blood flow during orthostasis in the heat-stressed human

Abstract

Given the large increase in cutaneous vascular conductance (CVC) during whole-body heat stress, this vascular bed is important in the regulation of blood pressure during orthostatic stress. In this thermal state, changes in CVC are reported to be due to withdrawal of active vasodilator activity. The purpose of this study was to identify, contrary to the current line of thinking, whether cutaneous vasoconstrictor neural activity is enhanced and capable of contributing to reductions in CVC during an orthostatic challenge of heat-stressed individuals. Healthy normotensive subjects were pretreated, subcutaneously, with botulinum toxin A (BTX-A) to inhibit the release of neurotransmitters from cutaneous active vasodilator nerves. On the experimental day, microdialysis probes were placed in the BTX-A-treated site and in an adjacent untreated site. In protocol 1, internal temperature was elevated approximately 0.7 degrees C, followed by the application of lower body negative pressure (LBNP; -30 mmHg). LBNP reduced CVC at the BTX-A-treated sites (Delta4.2 +/- 2.9%max), as well as at the control site (Delta9.8 +/- 4.1%max). In protocol 2, after confirming the absence of cutaneous vasodilatation at the BTX-A-treated site during whole-body heating, CVC at this site was elevated to a similar level relative to the control site (55.4 +/- 13.4 versus 60.7 +/- 10.4%max, respectively) via intradermal administration of isoproterenol prior to LBNP. Similarly, when flow was matched between sites, LBNP reduced CVC at both the BTX-A-treated (Delta15.3 +/- 4.6%max) and the control sites (Delta8.8 +/- 5.6%max). These data suggest that the cutaneous vasoconstrictor system is engaged and is capable of decreasing CVC during an orthostatic challenge in heat-stressed individuals.

Figure 1. Cutaneous vascular conductance (CVC) responses during whole-body heat stress followed by lower body negative pressure (LBNP) at the control (○) and the BTX-A-treated (•) sites for protocol 1

Whole-body heating significantly increased CVC at the control site, whereas CVC at the BTX-A-treated site was only slightly increased. LBNP significantly reduced CVC at both sites.

Figure 2. Depiction of the methods used for protocol 2

Skin blood flow was assessed at both a control and BTX-A-treated site. Subjects were first exposed to a cold stress (CS) to confirm an intact vasoconstrictor system at both sites. Subjects were then exposed to whole-body heating. Upon identification of a successful blockade at the BTX-A-treated site, isoproterenol (ISO) was administered at this site to increase skin blood flow to a level similar relative to the control site. Subjects were then exposed to lower body negative pressure (LBNP).

Figure 3. Cutaneous vascular conductance (CVC) responses during the procedures outlined in protocol 2

Upon identification of an effective blockade at the BTX-A-treated site (labelled pre-ISO), the β-adrenergic agonist isoproterenol (ISO) was infused through the microdialysis membrane at that site to increase skin blood flow to a similar level relative to the control site (labelled pre-LBNP). Subjects were then exposed to lower body negative pressure (LBNP). LBNP significantly decreased CVC at both sites.

Figure 4. Changes in cutaneous vascular conductance (CVC) during lower body negative pressure (LBNP) for protocol 2

CVC decreased at the control and BTX-A + isoproterenol-treated sites, however, the reduction in CVC was significantly greater at the BTX-A + isoproterenol-treated site. Baseline values prior to LBNP are shown at the top of each column. There were no significant differences between baseline values (i.e. prior to LBNP). *Significantly different relative to the control site, P < 0.05.