Medow Marvin S, Glover June L, Stewart Julian M
Department of Pediatrics, New York Medical College, Valhalla, New York 10532, USA.
Microcirculation. 2008 Aug;15(6):569-79. doi: 10.1080/10739680802091526.
Acetylcholine-induced endothelium-dependent vasodilation in conduit arteries primarily depends on nitric oxide (NO). However, the biochemical mediators in the microvasculature remain less well defined. We tested whether prostaglandins and NO are responsible for cutaneous acetylcholine-mediated vasodilation and if they interact to modulate vasodilation. We measured skin blood flow (SBF) using laser Doppler flow (LDF) with intradermal microdialysis in the calves of 23 healthy volunteers. We examined the response of SBF to different doses of acetylcholine (0.01-100 mM), the nonisoform-specific NO synthase inhibitor, nitro-L-arginine (NLA, 10 mM), the nonspecific cyclo-oxygenase (COX) inhibitor, ketorolac (Keto, 10 mM), and combined NLA + Keto. NLA had no effect on baseline SBF, while Keto increased baseline SBF by approximately 150%. The increase was blunted with combined NLA + Keto. SBF increased by approximately 700% with the highest acetylcholine concentration and reduced by approximately 60% by NLA. Ketorolac alone also reduced the response to acetylcholine, although the reduction varied between 10 and 20% at differing acetylcholine doses. NLA plus ketorolac reduced the responses to different doses of acetylcholine by some 30%, which was intermediate to NOS or COX inhibition alone. These data suggest that cutaneous acetylcholine-mediated endothelium-dependent vasodilation is highly NO-dependent and is also strongly related to the interactions of NO with prostaglandins.
在传导动脉中，乙酰胆碱诱导的内皮依赖性血管舒张主要依赖于一氧化氮（NO）。然而，微血管中的生化介质仍不太明确。我们测试了前列腺素和NO是否参与皮肤乙酰胆碱介导的血管舒张，以及它们是否相互作用来调节血管舒张。我们使用激光多普勒血流仪（LDF）结合皮内微透析技术，测量了23名健康志愿者小腿的皮肤血流量（SBF）。我们研究了SBF对不同剂量乙酰胆碱（0.01 - 100 mM）、非异构体特异性一氧化氮合酶抑制剂硝基-L-精氨酸（NLA，10 mM）、非特异性环氧化酶（COX）抑制剂酮咯酸（Keto，10 mM）以及联合使用NLA + Keto的反应。NLA对基础SBF无影响，而Keto使基础SBF增加了约150%。联合使用NLA + Keto可减弱这种增加。最高浓度乙酰胆碱使SBF增加约700%，而NLA使其降低约60%。单独使用酮咯酸也可降低对乙酰胆碱的反应，尽管在不同乙酰胆碱剂量下降低幅度在10%至20%之间变化。NLA加酮咯酸使对不同剂量乙酰胆碱的反应降低约30%，这介于单独抑制NOS或COX之间。这些数据表明，皮肤乙酰胆碱介导的内皮依赖性血管舒张高度依赖NO，并且也与NO和前列腺素的相互作用密切相关。
