Rasmussen Carol A, Gabelt B'Ann True, Kaufman Paul L
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.
Trans Am Ophthalmol Soc. 2007;105:225-38; discussion 238-9.
To determine the effects of the kappa opioid agonist, bremazocine (BRE), on intraocular pressure (IOP) and aqueous humor dynamics in normotensive cynomolgus monkeys.
IOP, pupil diameter, refraction, aqueous humor flow, and mean arterial pressure (MAP) were measured following unilateral topical application of 1 to 100 microg BRE. IOP and MAP responses to 100 microg BRE were repeated during intravenous infusion of angiotensin II (ATII). IOP and MAP responses to BRE were also measured following pretreatment with the opioid receptor antagonists norbinaltorphimine (nor-BNI) or naloxone. Outflow facility was measured following unilateral intracameral exchange with 0.01 to 100 microg/mL BRE. IOP, aqueous humor flow, pupil, and MAP were measured after unilateral intracameral bolus injection of 1 microg of BRE.
Unilateral topical BRE caused a dose-related reduction in IOP and aqueous humor flow in both eyes and in MAP. Pupil miosis occurred at the 100-microg dose. There was no effect on refraction. IOP and MAP decreases after 100 microg of BRE were eliminated by ATII infusion. Differential IOP effects after 10-microg topical BRE doses were not eliminated by nor-BNI or naloxone. Unilateral intracameral bolus injection of BRE decreased IOP in both eyes but had no effect on MAP or aqueous humor flow. Outflow facility was unchanged after intracameral exchange with BRE.
The IOP response to high doses of BRE in monkeys can be attributed to peripheral or central effects on MAP. The IOP-lowering response to topical BRE is due to aqueous humor flow suppression via non-opioid receptor stimulation. Some components of the IOP response are mediated by unknown mechanisms.
确定κ阿片受体激动剂布瑞马佐辛(BRE)对正常血压食蟹猴眼压(IOP)和房水动力学的影响。
在单侧局部应用1至100微克BRE后,测量IOP、瞳孔直径、屈光、房水流量和平均动脉压(MAP)。在静脉输注血管紧张素II(ATII)期间,重复测量对100微克BRE的IOP和MAP反应。在用阿片受体拮抗剂诺宾那托啡(nor-BNI)或纳洛酮预处理后,也测量对BRE的IOP和MAP反应。在单侧前房内用0.01至100微克/毫升BRE置换后,测量房水流畅系数。在单侧前房内推注1微克BRE后,测量IOP、房水流量、瞳孔和MAP。
单侧局部应用BRE导致双眼IOP、房水流量和MAP呈剂量相关的降低。在100微克剂量时出现瞳孔缩小。对屈光无影响。输注ATII消除了100微克BRE后的IOP和MAP降低。10微克局部BRE剂量后的IOP差异效应未被nor-BNI或纳洛酮消除。单侧前房内推注BRE降低了双眼的IOP,但对MAP或房水流量无影响。前房内用BRE置换后,房水流畅系数未改变。
猴子对高剂量BRE的IOP反应可归因于对MAP的外周或中枢作用。局部应用BRE降低IOP的反应是由于通过非阿片受体刺激抑制房水流量。IOP反应的一些成分是由未知机制介导的。