Microvascular responses to common endothelial stimuli are not related in humans

Background: Cutaneous microvascular responses to local heating and acetylcholine perfusion are widely used to assess nitric oxide (NO)-mediated endothelium-dependent dilation in human health and disease. Despite the increasingly common usage of these approaches, no studies have directly compared responses to these stimuli within individuals. Therefore, we assessed endothelium- and NO-dependent dilation in 80 young adults (40 males/40 females; 22{+/-}3 years) to determine the extent to which microvascular responses to these endothelium-dependent stimuli are comparable within an individual. Methods: We examined cutaneous vascular conductance responses to (1) standardized local heating protocols to 39{degrees}C and 42{degrees}C, and (2) graded infusions of acetylcholine (10-10-10-1 M) alone or with 15 mM NG-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor). Endothelium- and NO-dependent dilation were calculated and expressed in multiple ways based on commonly published analyses to allow for a thorough comparison within and between each stimulus. Results: Local heating-induced endothelium- and NO-dependent dilation were lower at 39{degrees}C compared with 42{degrees}C (P<0.001). The magnitude of local heating-induced endothelium-dependent dilation was significantly related to the NO-dependent contribution of that response at 39{degrees}C (R2= 0.79) and 42{degrees}C (R2= 0.56). Local heating-induced NO-dependent dilation at 39{degrees}C was not related to that at 42{degrees}C (P>0.05). Acetylcholine-induced endothelium- and NO-dependent dilation were not related to local heating-induced responses (all P>0.05). Conclusions: These data demonstrate that while local heating and acetylcholine perfusion produce robust endothelium- and NO-dependent cutaneous vasodilation, these responses are not comparable within an individual.