Rosa Robert H, Hein Travis W, Yuan Zhaoxu, Xu Wenjuan, Pechal Melissa I, Geraets Ryan L, Newman Joseph M, Kuo Lih
Department of Opthamology and Surgery, Scott and White Eye Institute, Texas A & M University System Health Science Center, Temple, TX 76508, USA.
Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H231-8. doi: 10.1152/ajpheart.01281.2005. Epub 2006 Feb 17.
Brimonidine, an alpha2-adrenergic receptor (AR) agonist, has been employed in the treatment of glaucoma due to its beneficial effects on intraocular pressure reduction and neuroprotection. In addition, some studies have implicated that brimonidine might influence ocular blood flow; however, its effect on the retinal microcirculation has not been documented. Herein, we examined the vasomotor action of brimonidine on different branching orders of retinal arterioles in vitro and determined the contribution of the alpha2-AR subtype and the role of endothelium-derived nitric oxide (NO) in this vasomotor response. First- and second-order retinal arterioles of pigs were isolated, cannulated, and pressurized for functional studies. Videomicroscopic techniques were employed to record diameter changes in response to brimonidine. RT-PCR was performed for detection of alpha-AR and endothelial NO synthase (eNOS) mRNA in retinal arterioles. All first-order arterioles (82 +/- 2 microm ID) dilated dose dependently to brimonidine (0.1 nM to 10 microM) with 10% dilation at the highest concentration. Second-order arterioles (50 +/- 1 microm ID) responded heterogeneously with either dilation or constriction. The incidence and magnitude of vasoconstriction were increased with increasing brimonidine concentration. Administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester abolished the brimonidine-induced vasodilation in first- and second-order arterioles. Regardless of vessel size, vasomotor responses (i.e., vasodilation and vasoconstriction) of retinal arterioles were sensitive to the alpha2-AR antagonist rauwolscine. Consistent with the functional data, alpha2A-AR and eNOS mRNAs were detected in retinal arterioles. Collectively, our data demonstrate that brimonidine at clinical doses evokes a consistent NO-dependent vasodilation in first-order retinal arterioles but a heterogeneous response in second-order arterioles. These vasomotor responses are mediated by the activation of alpha2-AR. It appears that brimonidine, depending on the concentration and vessel size, may alter local retinal blood flow.
溴莫尼定是一种α2 - 肾上腺素能受体（AR）激动剂，因其在降低眼压和神经保护方面的有益作用，已被用于青光眼的治疗。此外，一些研究表明溴莫尼定可能会影响眼部血流；然而，其对视网膜微循环的影响尚未见报道。在此，我们在体外研究了溴莫尼定对不同分支等级视网膜小动脉的血管舒缩作用，并确定了α2 - AR亚型的作用以及内皮源性一氧化氮（NO）在这种血管舒缩反应中的作用。分离猪的一级和二级视网膜小动脉，插管并加压进行功能研究。采用视频显微镜技术记录对溴莫尼定的直径变化。进行逆转录聚合酶链反应（RT-PCR）检测视网膜小动脉中α - AR和内皮型一氧化氮合酶（eNOS）mRNA。所有一级小动脉（内径82±2微米）对溴莫尼定（0.1纳摩尔至10微摩尔）呈剂量依赖性舒张，在最高浓度时舒张10%。二级小动脉（内径50±1微米）反应各异，既有舒张也有收缩。随着溴莫尼定浓度增加，血管收缩的发生率和幅度增加。给予一氧化氮合酶抑制剂NG - 硝基 - L - 精氨酸甲酯可消除溴莫尼定在一级和二级小动脉中诱导的血管舒张。无论血管大小，视网膜小动脉的血管舒缩反应（即血管舒张和血管收缩）对α2 - AR拮抗剂萝芙木碱敏感。与功能数据一致，在视网膜小动脉中检测到α2A - AR和eNOS mRNA。总体而言，我们的数据表明，临床剂量的溴莫尼定在一级视网膜小动脉中引起一致的依赖NO的血管舒张，但在二级小动脉中反应各异。这些血管舒缩反应由α2 - AR的激活介导。似乎溴莫尼定根据浓度和血管大小可能会改变局部视网膜血流。
