Majmudar N G, Anumba D, Robson S C, Ford G A
Department of Pharmacological Sciences, University of Newcastle Upon Tyne, United Kingdom.
Br J Clin Pharmacol. 1999 Feb;47(2):173-7. doi: 10.1046/j.1365-2125.1999.00880.x.
beta2-adrenoceptor agonists are generally considered to produce endothelium independent vasodilatation through adenylate cyclase. We determined whether nitric oxide contributes to beta2-adrenoceptor vasodilatation in human arterial vasculature.
Forearm blood flow responses to brachial intra-arterial infusions of ritodrine (2.5-50 microg min(-1)), a selective beta2-adrenoceptor agonist, were determined in 24 healthy, normotensive subjects (mean age 22 years, 5F) on two occasions with initial and concomitant administration of L-NMMA (800 microg min(-1)), an NO synthase inhibitor, or noradrenaline (5-30 ng min(-1)), a control constrictor not affecting basal NO activity. Responses to the endothelium dependent vasodilator scrotonin (n = 6) and an endothelium independent vasodilator GTN (n = 9) were also determined.
Maximal dilatation to ritodrine during L-NMMA infusion (310+/-32%; mean+/-s.e.mean) was reduced compared to that during noradrenaline infusion (417+/-41%, P<0.05), as were summary responses (1023+/-101 vs 1415+/-130; P<0.05). Responses to GTN were unaffected by L-NMMA compared to noradrenaline; max 177+/-26 vs 169+/-20%, 95% CI for difference -33,48; P=0.68; summary response 361+/-51 vs 396+/-37, 95% CI -142,71; P=0.46. Dilator responses to serotonin were reduced by L-NMMA; max 64+/-20 vs 163+/-26%, P<0.01; summary response 129+/-36 vs 293+/-60; P<0.05) and to a greater extent than ritodrine (58+/-7 vs 25+/-14%, P<0.05).
beta2-adrenoceptor mediated vasodilatation in the human forearm has an NO mediated component. The underlying mechanism for this effect is unclear, but flow mediated vasodilatation is unlikely to be responsible.
β2 - 肾上腺素能受体激动剂通常被认为通过腺苷酸环化酶产生不依赖内皮的血管舒张作用。我们确定一氧化氮是否在人体动脉血管系统中对β2 - 肾上腺素能受体介导的血管舒张起作用。
在24名健康、血压正常的受试者（平均年龄22岁，5名女性）中，分两次测定前臂血流对肱动脉内输注利托君（一种选择性β2 - 肾上腺素能受体激动剂，剂量为2.5 - 50微克·分钟−1）的反应，第一次单独给药，第二次同时给予一氧化氮合酶抑制剂L - NMMA（800微克·分钟−1）或去甲肾上腺素（5 - 30纳克·分钟−1，一种不影响基础一氧化氮活性的对照缩血管剂）。还测定了对内皮依赖性血管舒张剂血清素（n = 6）和内皮非依赖性血管舒张剂硝酸甘油（n = 9）的反应。
与去甲肾上腺素输注期间相比，L - NMMA输注期间对利托君的最大舒张反应（310±32%；平均值±标准误平均值）降低（417±41%，P<0.05），总反应也降低（1023±101对1415±130；P<0.05）。与去甲肾上腺素相比，L - NMMA对硝酸甘油的反应无影响；最大舒张反应177±26%对169±20%，差异的95%置信区间为 - 33,48；P = 0.68；总反应361±51对396±37，95%置信区间为 - 142,71；P = 0.46。L - NMMA使对血清素的舒张反应降低；最大舒张反应64±20%对163±26%，P<0.01；总反应129±36对293±60；P<0.05），且降低程度大于对利托君的反应（58±7%对25±14%，P<0.05）。
人体前臂中β2 - 肾上腺素能受体介导的血管舒张有一氧化氮介导的成分。这种作用的潜在机制尚不清楚，但血流介导的血管舒张不太可能是原因。
