Pharmacological effect of Neuropeptides on ciliary artery smooth muscle cells

为了阐明不同抗青光眼药物的血管扩张机制，我们观察了左旋布洛尔和前列腺素类似物对体外培养的兔睫状动脉的作用。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。用荧光分光光度法研究了相同药物对培养的人主动脉平滑肌细胞内游离钙离子浓度的影响。用高K液、1μM组胺、10μM苯肾上腺素或10 0nM内皮素-1使睫状动脉松弛。内皮型一氧化氮合酶的抑制或内皮的剥离不影响这种松弛。实验结果表明，左旋布洛尔可通过两种不同的机制松弛兔睫状动脉。首先，放松可能是由于通过…封锁了钙离子进入更多不依赖电压的钙离子通道。其次，来昔布洛尔可能改变血管平滑肌细胞的钙敏感性。他氟前列素对高K液预收缩的兔眼睫状动脉具有浓度依赖性的松弛作用。他氟前列素的作用强于前列腺素E_2(PGE_2)或前列腺素I_2(PGI_2)。他氟前列素对兔睫状动脉平滑肌的松弛作用可能至少部分是由于抑制了细胞外钙离子的容量性内流。许多抗青光眼药物对离体兔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 levobunolol and prostaglandin analogs 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. The effects of the same agents on intracellular free calcium ([Ca^<2+>]I) in cultured human aortic smooth muscle cells were also studied by fluorophotometry. Levobunolol relaxed ciliary artery pre-contracted with either high-K solution, 1 μM histamine, 10 μM phenylephrine, or 100 nM endothelin-1. Inhibition of endothelial nitric oxide synthase or denudation of the endothelium did not affect this relaxation. Experimental results indicate that levobunolol may relax rabbit ciliary artery by two different mechanisms. First, the relaxation could be due to the blockade of Ca^<2+> entry thr … More ough non voltage-dependent Ca^<2+> channels. Second, lecobunolol may change the Ca^<21> sensitivity of vascular smooth muscle cells. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries pre-contracted with a high-K solution. Tafluprost was more potent than prostaglandin E_2 (PGE_2) or prostaglandin I_2 (PGI_2). Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca^<2+> entry from the extracellular space. 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