Nitric Oxide-Dependent Cutaneous Vasodilation in Young Adults: a Comparison of In Vivo Methodological Approaches

• Joy Mochache, Nutritional Science, University of Delaware

• Jody Greaney, Department of Health Behavior and Nutrition Sciences, University of Delaware

Nitric Oxide-Dependent Cutaneous Vasodilation in Young Adults: a Comparison of In Vivo Methodological Approaches

Joy Mochache, Navyasree Vadlamudi, Aaron Autler, and Jody Greaney

A reduction in nitric oxide (NO)-mediated endothelium-dependent vasodilation is a primary antecedent of atherosclerotic cardiovascular disease. Because endothelial dysfunction is thought to first occur in the cutaneous microvasculature, quantifying NO-dependent vasodilation in this microcirculatory bed is clinically relevant. Historically, rapid local heating to 42°C was considered the standard approach to assess cutaneous microvascular NO bioavailability. More recently, some have adopted rapid local heating to 39°C instead, based on its purported larger dependency on NO. However, to date, no studies have rigorously examined or compared the quantification of NO-dependent vasodilation using both physiological and pharmacological approaches. We hypothesized that NO-dependent vasodilation in response to local heating to 39°C would be greater than heating to 42°C and that the NO-dependent portion of vasodilation in response to local heating would be greater than that that in response to pharmacological stimulation with acetylcholine (ACh). Using intradermal microdialysis coupled with laser Doppler, red cell flux was measured during 1) rapid local skin heating to either 39°C or 42°C, followed by perfusion of the nonspecific NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME; 15 mM) and 2) graded intradermal microdialysis perfusion of ACh alone and in combination with NO synthase inhibition in 6 young adults (5F; 21±3 yrs). The NO-dependent component of the vasodilatory response to these stimuli was during rapid local heating to 42°C (42°C: 66±13%; 39°C: 39±10%; ACh: 23±29%). Consistent with recent calls for improved rigor and reproducibility in biomedical science, the data generated from this project (target n=80) are expected to provide novel insight for study design and data interpretation when comparing cutaneous NO-dependent vasodilation between different groups, conditions, or studies, as well as before and after interventions/treatments.