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Effects and Interactions of Nitric Oxide and Prostaglandins during Acetylcholine Mediated Cutaneous Vasodilation in Humans
Author(s) -
Medow Marvin Scott,
Goligorsky Michael S.,
Glover June L.,
Stewart Julian M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1298-b
Subject(s) - acetylcholine , vasodilation , nitric oxide , microdialysis , chemistry , endocrinology , medicine , pharmacology , nitric oxide synthase , prostaglandin , extracellular , biochemistry
Endothelium‐dependent vasodilation produced by acetylcholine in conduit arteries primarily depends on nitric oxide (NO). However, the biochemical mediators in the microvasculature remain less well defined. We tested the hypothesis that prostaglandins as well as NO are responsible for cutaneous acetylcholine mediated vasodilation and that NO and prostaglandins interact to exert modulatory effects on this response. To accomplish this we performed experiments using laser Doppler flow (LDF) combined with intradermal microdialysis in the calves of 23 healthy volunteers aged 19‐27 years. We examined the response to different doses of acetylcholine (0.01mM to 100mM) using LDF as the response parameter. We tested the effects of the non‐isoform specific NO synthase inhibitor nitro‐L‐arginine (NLA, 10mM), the nonspecific cycloxygenase inhibitor ketorolac (Keto,10mM) and combined NLA+Keto on the LDF response to acetylcholine. NLA had no effect on baseline cutaneous flow, while Keto increased baseline flow by approximately 150%. The increase was blunted but present with combined NLA+Keto. LDF increased by approximately 700% with the highest concentration of acetylcholine tested. This increase was reduced approximately 60% by NLA. The decrease varied with the dose of acetylcholine. Adding Keto to NLA blunted the decrease in dose‐response. Ketorolac alone also reduced the response to acetylcholine although the reduction varied between 10‐20% at differing acetylcholine doses. These data suggest that cutaneous acetylcholine mediated endothelium‐dependent vasodilation is highly nitric oxide dependent and is also strongly related to the interactions of NO with prostaglandins.