The Action of Drugs on the Outflow of Aqueous Humour in the Rabbit

Anderson, Lorraine (1986) The Action of Drugs on the Outflow of Aqueous Humour in the Rabbit. PhD thesis, University of Glasgow.

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Although adrenaline has been reported to lower intraocular pressure (IOP) in both the conscious and anaesthetised rabbit the mechanism and adrenoceptor(s) involved in this hypotensive response are unclear. In the conscious rabbit topically applied adrenaline produced a biphasic pressure response, an initial hypertensive response followed by the expected but longer lasting hypotensive response. Adrenaline also produced mydriasis, an alpha adrenoceptor mediated response. The mechanism whereby adrenaline lowers IOP was investigated by measuring the facility of outflow of aqueous humour from the anterior chamber of the anaesthetised rabbit using a constant pressure anterior chamber perfusion technique. Topically applied adrenaline raised facility of outflow and lowered IOP. Adrenaline produced its expected mydriasis. To date the majority of evidence suggest that adrenaline lowers IOP by acting via a beta adrenoceptor. Timolol was used as a pharmacological tool in the present experiments to investigate the involvement of the beta adrenoceptor in the outflow response to adrenaline. Timolol largely reversed the outflow response to adrenaline. All of the afore mentioned results imply that adrenaline lowers IOP by raising facility of outflow, an effect mediated via a beta adrenoceptor since it was reversed by timolol. Indomethacin, an inhibitor of prostaglandin (PG), biosynthesis can antagonise the ocular hypotensive response to chronic adrenaline treatment in the conscious rabbit. In the present experiments topical indomethacin pretreatment markedly antagonised the rise in facility of outflow and resultant fall in IOP caused by acute topical adrenaline treatment in the anaesthetised and conscious rabbit. This result suggested that following the interaction with beta adrenoceptors, PGs were involved at some stage in the outflow and pressure responses to adrenaline. Since indomethacin has known calcium antagonistic properties, the effects of aspirin and piroxicam, whose subsidiary properties differ from those of indomethacin, on the outflow and pressure responses to adrenaline were investigated. Systemic aspirin pretreatment had no affect on the ocular responses to adrenaline or their antagonism by indomethacin in the anaesthetised rabbit. The lack of an inhibitory effect by aspirin, be it through inhibition of PG. biosynthesis, or calcium antagonism, was perhaps explained by the comparitively low plasma levels of salicylic acid. Alternatively, the ability of aspirin to inhibit ocular biosynthesis may differ from that in other organs. Piroxicam is a potent inhibitor of PG biosynthesis at concentrations which have no effect on calcium fluxes. Topical piroxicam pretreatment antagonised the adrenaline-induced rise in facility of outflow and fall in IOP in the anaesthetised rabbit. This result lends weight to the theory that indomethacin antagonises the outflow response to adrenaline by blocking PG synthesis and not by inhibiting calcium movements. Nonetheless the effects of verapamil, a calcium channel blocker, on the pressure responses to adrenaline were investigated. Although topical verapamil pretreatment partially inhibited the hypertensive response (which may be the result of extraocular muscle contraction) to adrenaline the hypotensive response was unaltered. Again this result strengthens the hypothesis that adrenaline interacts on the beta adrenoceptor which at some stage results in the production of PGs which in turn could be responsible for the rise in facilty of outflow and consequent fall in IOP. This is also consistent with other workers' demonstration that low concentrations of PGs can both raise facility of outflow and lower IOP. Measuring PG concentrations in the aqueous humour was a more direct way of investigating the possible involevement of PGs in the ocular response to adrenaline. In the present experiments PG concentrations in the aqueous humour were measured using radioimmunoussay. Unfortunately this assay could neither accurately measure the very low concentrations of PGs present in aqueous humour samples nor distinguish differences in PG concentrations before and after drug treatment. The relevance of this work to the human eye has recently been confirmed by a report showing that systemic indomethacin reduces the hypotensive response to chronic adrenaline treatment in glaucoma patients. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Pharmacology, Ophthalmology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-77436
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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