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GABAergic control of arteriolar diameter in the rat retina

机译:GABA能控制大鼠视网膜小动脉直径

摘要

Purpose: To investigate the role of γ-aminobutryic acid (GABA) in the regulation of arteriolar diameter in the rat retina.Methods.: The actions of GABA on arteriolar diameter were examined using ex vivo retinal whole-mount preparations and isolated vessel segments. In most experiments, arterioles were partially preconstricted with endothelin (Et)-1. The expression levels of GABAA and GABAB receptors on isolated rat retinal Müller cells were assessed by immunohistochemistry.Results.: GABA (0.1–1 mM) evoked vasodilation or vasoconstriction of arterioles in whole-mount preparations. No such effects were observed with isolated vessel segments. In whole mount samples, the GABAA receptor agonist muscimol caused vasomotor responses in only a small proportion of vessels. In contrast, arteriolar responses to the GABAB receptor agonists baclofen and SKF97541 more closely resembled those observed with GABA. No responses were seen with the GABAC receptor agonist 5-methylimidazoleacetic acid. GABA-induced vasodilator responses were, for the most part, repeatable in the presence of the GABAA receptor antagonist bicuculline. These responses, however, were completely blocked in the presence of the GABAB receptor inhibitor 2-hydroxysaclofen. Strong immunolabeling for both GABAA and GABAB receptors was detected in isolated Müller cells. In the absence of Et-1–induced preconstriction, most vessels were unresponsive to bicuculline or 2-hydroxysaclofen.Conclusions.: GABA exerts complex effects on arteriolar diameter in the rat retina. These actions appear largely dependent upon the activation of GABAB receptors in the retinal neuropile, possibly those located on perivascular Müller cells. Despite these findings, endogenous GABA appears to contribute little to the regulation of basal arteriolar diameter in the rat retina.
机译:目的:探讨γ-氨基丁酸(GABA)在大鼠视网膜小动脉直径调节中的作用。方法:采用离体视网膜全量制剂和离体血管段,研究了GABA对小动脉直径的作用。在大多数实验中,小动脉部分被内皮素(Et)-1预收缩。通过免疫组织化学评估离体大鼠视网膜Müller细胞上GABAA和GABAB受体的表达水平。结果:GABA(0.1–1 mM)引起整装制剂中小动脉的血管舒张或血管收缩。用隔离的血管段未观察到这种影响。在整个样本中,GABAA受体激动剂麝香酚仅在一小部分血管中引起血管舒缩反应。相反,对GABAB受体激动剂巴氯芬和SKF97541的小动脉反应与用GABA观察到的反应更相似。 GABAC受体激动剂5-甲基咪唑乙酸未见反应。在存在GABAA受体拮抗剂bicuculline的情况下,GABA诱导的血管舒张反应在大多数情况下是可重复的。但是,在存在GABAB受体抑制剂2-羟基沙氯芬的情况下,这些反应被完全阻断。在分离的Müller细胞中检测到针对GABAA和GABAB受体的强免疫标记。在没有Et-1引起的前收缩的情况下,大多数血管对双瓜氨酸或2-羟基沙氯芬没有反应。结论:GABA对大鼠视网膜的小动脉直径具有复杂的作用。这些作用在很大程度上取决于视网膜神经堆中GABA B受体的激活,可能是位于血管周围Müller细胞上的那些受体。尽管有这些发现,内源性GABA似乎对大鼠视网膜基底小动脉直径的调节几乎没有贡献。

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