Dorner Guido T, Garhöfer Gerhard, Huemer Karl-Heinz, Golestani Elisabeth, Zawinka Claudia, Schmetterer Leopold, Wolzt Michael
Department of Clinical Pharmacology, Allgemeines Krankenhaus Vienna, Vienna, Austria.
Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3947-51. doi: 10.1167/iovs.02-0855.
Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo.
The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days.
Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion.
Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.
肾上腺髓质素作为一种血管舒张剂,可能在眼部炎症过程中发挥作用。本研究旨在确定一氧化氮的形成是否参与体内眼部血管系统对肾上腺髓质素的反应。
在初步研究(n = 7)中,通过测量眼底搏动幅度和黄斑区的激光多普勒血流,评估全身静脉注射肾上腺髓质素(3.2 - 16.0 pmol/[kg·min])对脉络膜血流的影响,并通过超声多普勒血流评估其对眼动脉血流的影响。随后,在一项双盲随机安慰剂对照交叉研究中,对8名健康男性受试者研究了12.8 pmol/(kg·min)肾上腺髓质素对眼部和全身血流动力学的影响。在不同的研究日,将肾上腺髓质素与一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸(3 mg/kg推注和30 μg/[kg·min]持续静脉输注)或载体对照共同输注。
肾上腺髓质素剂量依赖性地增加脉络膜血流和眼动脉血流速度。N(G)-单甲基-L-精氨酸降低了肾上腺髓质素对眼底搏动幅度的影响,但未改变眼动脉的血流反应。肾上腺髓质素输注对全身血流动力学无影响。
眼部血流对肾上腺髓质素浓度变化敏感。肾上腺髓质素的急性血管舒张作用在脉络膜中依赖一氧化氮,但在眼动脉中不依赖。