Endothelium‐dependent cutaneous vasodilation in young smokers: role of endothelial‐derived hyperpolarizing factors

Abstract

In young humans, endothelium‐dependent cutaneous vasodilation (EDCV) relates to both nitric oxide (NO) and cyclooxygenase (COX) pathways. We have recently shown that endothelial‐derived hyperpolarizing factors (EDHFs) are also involved, and that young smokers have impaired EDCV due to diminished NO‐ and COX‐dependent vasodilation. In this study, we tested the hypothesis that EDHFs greatly contribute to EDCV in young smokers to compensate for the lack of NO‐ and COX‐dependent vasodilation. We evaluated the increase in cutaneous vascular conductance (CVC) from baseline to peak value (CVCΔpeak) during acetylcholine (ACh) infusions of 1, 10, and 100mM at four intradermal microdialysis sites: 1) Ringer (control), 2) tetraethylammonium (TEA, a calcium‐sensitive potassium channel blocker which prevents EDHF‐induced vasodilation), 3) Nω‐Nitro‐L‐arginine (L‐NNA, NO synthase inhibitor) + Ketorolac (Keto, COX inhibitor), and 4) combination of TEA, L‐NNA, and Keto. At 100mM of ACh, CVCΔpeak at Ringer sites (54.4±14.2%max) was higher than that at the TEA sites (37.8±17.8%max), but was similar to that at the L‐NNA + Keto sites (57.5±1.3%max). Similar results were also obtained with 1 and 10 mM ACh. These data suggest that NO and COX pathways are deficient in EDCV of young smokers, but that a significant EDHF component remains.Grant: NIH HL081671