Pharmacological effects of various ant-glaucoma agents on rabbit ciliary artery

为了阐明各种抗青光眼药物的血管扩张机制，我们研究了这些药物对体外培养的兔眼睫状动脉的作用。在解剖显微镜下，从白化兔眼制备睫状动脉，并将其安装在肌图仪系统中。用等长张力记录法研究了不同试剂的作用效果。给予匹罗卡品可产生剂量依赖性的肌肉松弛，这种松弛可被L-NAME、1μM阿托品或剥离内皮细胞所消除。我们的结论是，这种松弛依赖于内皮和NO的合成。倍他洛尔或噻吗洛尔的应用呈剂量依赖性地引起松弛。据推测，这种松弛是通过类似于钙拮抗剂的作用发生的。乌诺前列酮对高钾溶液预收缩的睫状动脉具有剂量依赖性的松弛作用。这种松弛不依赖于腺酰环化酶、鸟苷酸环化酶或MAXI-K通道。RELAXA…更多的作用可能是通过抑制钙离子内流，可能是通过容量性钙离子通道。尼普拉地洛还引起睫状动脉的剂量依赖性松弛。研究表明，尼普拉地洛通过两种不同的机制松弛兔的睫状动脉。首先，这种松弛是由于尼普拉地洛本身反硝化产生的一氧化氮。第二，尼普拉地洛可能是一种α-肾上腺素能拮抗剂，许多抗青光眼药物对兔眼睫状动脉具有血管扩张作用，这些作用可能解释了体内眼部血流量增加的机制。然而，这些药物松弛睫状动脉的作用机制不同，与降眼压的作用机制也不同。虽然人们普遍认为眼压升高是青光眼的主要危险因素，但眼血管灌流在视神经损伤和视野丧失的发病机制中也起着重要作用，尤其是在正常眼压性青光眼患者中。因此，更好地了解各种抗青光眼药物对眼循环的影响，对于优化其临床应用具有重要意义。较少

To clarify the vasodilatory mechanism of various antiglaucoma ophthalmic agent, we have investigated the effect of these drugs on isolated rabbit ciliary artery in vitro. Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a myograph system. The effects of various agents were investigated using isometric tension recording methods. Pilocarpine administration produced a dose-dependent muscle relaxation that was abolished by treatment with L-NAME, 1μM atropine, or denudation of the endothelium. We concluded that This relaxation was dependent on the endothelium and NO synthesis. Application of betaxolol or timolol dose dependently provoked relaxation. Presumably, this relaxation occurs through action similar to Ca^<2+> antagonists. Unoprostone induced a dose-dependent relaxation in ciliary arteries that were pre-contracted with high-K solution. The relaxation does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxa … More tion may be mediated by inhibition of Ca^<2+> entry, possibly through capacitative Ca^<2+> channels. Nipradilol also provoked a dose-dependent relaxation in ciliary arteries. Investigations have revealed that nipradilol relaxes rabbit ciliary artery by two different mechanisms. First, the relaxation is due to the nitric oxide produced by denitrification of nipradilol itself. Second, nipradilol may act as an a-adrenergic antagonist.Many anti-glaucoma agents have vasodilatory effect on isolated rabbit ciliary artery These actions may explain the mechanisms of increased ocular blood flow in vivo. However, mechanisms of these drugs in relaxing ciliary artery differ from each other and are also different from that of IOP reduction. Though it is generally accepted that increased intraocular pressure is a major risk factor in glaucoma, ocular vascular perfusion is also important in the pathogenesis of optic nerve damage and visual field loss, especially in patients with normal tension glaucoma. Therefore a better understanding of the effect of various antiglaucoma agents on ocular circulation is important for optimizing their clinical use. Less