Nitric oxide (NO) and oxygen (02) transport in the microcirculation are coupled in a complex manner, since enzymatic production of NO depends on O2 availability, NO modulates vascular tone and O2 delivery, and tissue O2 consumption is reversibly inhibited by NO. The authors investigated whether NO bioavailability is influenced by the well-known Fåhraeus effect, which has been observed for over 70 years. This phenomenon occurs in small-diameter blood vessels, where the tube hematocrit is reduced below systemic hematocrit as a plasma boundary layer forms near the vascular wall when flowing red blood cells (rbcs) migrate toward the center of the bloodstream. Since hemoglobin iii the bloodstream is thought to be the primary scavenger of NO in vivo, this might have a significant impact on NO transport. To investigate this possibility, the authors developed a multilayered mathematical model for mass transport in arterioles using finite element numerical methods to simulate coupled NO and O2 transport in the blood vessel lumen, plasma layer, endothelium, vascular wall, and surrounding tissue. The Fahraeus effect was modeled by varying plasma layer thickness while increasing core hematocrit based on conservation of mass. Key findings from this study are that (1) despite an increase in the NO scavenging rate in the core with higher hematocrit, the model predicts enhanced vascular wall arid tissue NO bioavailability due to the relatively greater resistance for NO diffusion through the plasma layer; (2) increasing the plasma layer thickness also increases the resistance for O2 diffusion, causing a larger PO2 gradient near the vascular wall and decreasing tissue O2 availability, although this can be partially offset with inhibition of O2 consumption by higher tissue NO levels; (3) the Fåhraeus effect can become very significant in smaller blood vessels (diameters <30 µm); and (4) models that ignore the Fãhraeus effect may underestimate NO concentrations in blood and tissue. Objective: To examine whether prostaglandins are involved in endotheliurn-dependent vasodilatory responses of the skin microcirculation. Methods: Twenty-three young male volunteers were studied on 2 different days 1-3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholirie (Ach, an endothelium-dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo-oxygenase inhibitor lysine acetylsalicylate (L-AS), 900 mg, or the oral intake of indornethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L-AS on skin reactive hyperemia were also assessed. Results: Acute cyclo-oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm²) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo-oxygenase inhibitor or not. For example, the mean response (+SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L-AS 339 ± 105, placebo 344 ± 68; with anesthesia: L-AS 453 + 76, placebo 452 + 65 (p < .01 for effect of anesthesia). Conclusions: These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism. [ABSTRACT FROM AUTHOR]