EDHFs contribute to ACh‐mediated vasodilation in human skin in a dose‐dependent manner

Abstract

The human cutaneous microcirculation has been shown to be reflective of globalized microvascular function, but the role of EDHFs in acetylcholine (ACh) mediated vasodilation has yet to be explored. In humans and animals, EDHFs appear to play only a modest role in ACh vasodilation, with a greater contribution at higher doses of ACh and under disease or NO‐deficient conditions. Five bolus doses of ACh (0.01, 0.1, 1, 10, and 100mM) were delivered via microdialysis fibers continuously infused with 1) Lactated Ringer's, 2) tetraethylammonium (TEA; calcium‐sensitive potassium channel & EDHF inhibitor), 3) L‐NNA + Ketorolac (to inhibit NO + COX), and 4) TEA + L‐NNA + Keto. The hyperemic response was characterized as area under the curve (AUC) and reported as % max cutaneous vascular conductance. In our preliminary findings (n=5), TEA had no effect on AUC compared to control at any of the lower doses of ACh, but did attenuate AUC to 100mM ACh (Control: 31,621±5,947% vs. TEA: 20,809±6,686%). We found similar results with combined NO + COX inhibition. TEA + L‐NNA + Keto did not attenuate AUC compared to L‐NNA + Keto until the 100mM dose of ACh (L‐NNA + Keto: 16,308±2831% vs. TEA + L‐NNA + Keto: 8,491±1,853%). Therefore, EDHFs appear to contribute to ACh vasodilation in the skin in a dose‐dependent manner, similarly to other vascular beds, confirming the skin to be a good model of overall microvascular function.Supported by NIH Grant HL081671