Cutaneous Endothelial Dependent and Independent Vascular Responsiveness after Prolonged Head-Down Bed Rest

Abstract

Spaceflight, or its ground based analog head-down bed rest (HDBR), reduces the elevation in skin blood flow to whole-body and local heating. The mechanisms that underlie these microgravity-related changes are unclear and may be related to altered cutaneous post-synaptic function (i.e., decreased sensitivity to vasodilator neurotransmitters and co-factors). PURPOSE: Test the hypothesis that HDBR alters post-synaptic cutaneous vascular responsiveness to endothelial-dependent and independent vasodilators. METHODS: Intradermal microdialysis membranes were placed in forearm skin of seven healthy subjects (5 males, 2 females) before and, in a randomised fashion, on day 16 or 18 of 6° HDBR, thereby allowing local delivery of the endothelial-dependent vasodilator, acetylcholine (ACh; 1x10-7 to 1x10-1 M at 10-fold increments) and the endothelial-independent nitric oxide donor, sodium nitroprusside (SNP; 5x10-8 to 5x10-2 M at 10-fold increments). Local skin temperature was clamped at 34 °C throughout the protocols. Cutaneous vascular conductance (CVC) was calculated from the ratio of laser-Doppler derived skin blood flux (assessed directly over the membranes) to mean arterial blood pressure. CVC dose-response curves to ACh and SNP were modeled via nonlinear regression curve fitting to identify the dose of ACh and SNP causing 50% of the maximal vasodilator response (EC50), used as an index of cutaneous vascular responsiveness. RESULTS: The EC50 of the ACh dose response curve was unchanged after HDBR (pre-HDBR: −3.71 ± 0.35 vs post HDBR: −3.82 ± 0.64 log M, P = 0.88) as was the EC50 of the SNP dose response curve (pre-HDBR: −3.98 ± 0.25 vs post HDBR: −4.37 ± 0.33 log M, P = 0.30). CONCLUSIONS: HDBR does not affect post-synaptic cutaneous endothelial dependent and independent responsiveness, as indexed by the EC50 of the assessed dose-response curves. Given these findings, reduced increases in skin blood flow during whole-body and local heating after HDBR are unlikely to be due to impaired endothelial dependent and independent vasodilator responsiveness. This research project was funded by grants from the National Heart, Lung and Blood Institute (HL-61388, HL-67422, HL-84072, GM-68865).