Ph. F. J. Hoyng

Does prostacyclin mediate alpha-adrenergic induced hypotension?

We have extended our previous observations on the effect of tranylcypromine (TCP) on intraocular pressure (IOP), following topical administration of catecholamines is normal and chemically denervated rabbit eyes. In normal eyes, TCP inhibits the hypotensive phase after topical norepinephrine (nE); less after epinephrine (E); and not at all after isoproterenol. In denervated eyes, the inhibitory effect of TCP on the hypotensive phase of nE and E is enhanced. Phenoxybenzamine (PBA), but not timolol maleate or indomethacin, blocks the effect of TCP on α-adrenergic induced hypotension.Prostacyclin-like activity was estimated by bioassay using ADP induced rat platelet aggregation. This activity is significantly reduced in the primary aqueous and in the iris after TCP but it is significantly increased in pooled data of aqueous samples after topical nE.We conclude that the inhibitory effect of TCP on the hypotensive phase after topical E and nE is the result of inhibition of prostacyclin synthesis and not of MAO inhibition nor blockade of α-receptors. It is possible that the normal production of prostacyclin by the iris and ciliary body maintains (lower) basal levels of IOP.

Behaviour of IOP and pupil size after topical tranylcypromine in the rabbit eye

Repeated topical administration of tranylcypromine (TCP) to adult rabbit eyes causes a transient rise in intraocular pressure (IOP) for one half hour and a dilatation of the pupil for more than two hours. These effects are blocked by phenoxybenzamin but not by timolol. Indomethacin blocks the rise in pressure but not the pupillary dilatation. Chemical denervation blocks both effects. The rise in IOP is not followed by a hypotensive phase. It is suggested that TCP has a dual effect on the eye. Firstly, TCP as a releaser of endogenous nor-epinephrine (nE) and as a monoamine oxydase inhibitor will induce accumulation of nE at the receptor-side which in turn probably stimulates the synthesis of PGs to raise IOP. Secondly, TCP as a prostacyclin synthase inhibitor may be responsible for the absence of a hypotensive response. This is strengthened by the finding that TCP inhibits the hypotensive response to nE but potentiates the dilatation of the pupil.

The aqueous humor dynamics and the biphasic response in intraocular pressure induced by guanethidine and adrenaline in the glaucomatous eye

Continuous administration of guanethidine (3%) and adrenaline (0.5%) in one eyedrop (GA) induced a biphasic response of intraocular pressure (IOP). In ten patients with primary open angle and seven glaucoma suspects treated with (GA) twice daily during a 7 month period, tonography, and tonometry were performed and the pupil diameter measured 3 and 8 h post-GA. The combined data of both groups in the hypertensive phase, showed an IOP increase of 2.8 mm Hg (P<0.05), an unchanged coefficient of the outflow, dilated pupil (1.73 mm) (P<0.005) and a 36% increase of aqueous humor production (P<0.02). The specific biphasic course of IOP during treatment with GA seems to be caused by fluctuations in aqueous humor production. The increase in aqueous rate during the hypertensive phase could be related to secondary (rebound) vasodilation in the ciliary body and/or to a transient disruption of the blood-aqueous barrier induced by release of prostaglandins.

The influence of topical prostaglandins on HSA-induced uveitis in the rabbit

In this study the effect of topical administration of prostaglandins (PGs) on a human serum albumin (HSA)-induced uveitis is evaluated. Topical prostaglandin E1 (PGE,) and prostaglandin F2α (PGF2α) partly inhibited hyperaemia and flare in the anterior chamber after the induction of immune complex uveitis. A marked increase in the cellular response was observed in the aqueous humour after topical PGE1 and PGF2α. Topical prostaglandins may decrease endogenous prostaglandin formation and reduce the prostaglandin-mediated inflammatory symptoms; on the other hand, they also stimulate the aqueous cellular response, possibly by facilitation of leukotriene formation.These results indicate that topical prostaglandins should not be used to treat immunogenic uveitis.

Guanethidine — adrenaline eye drops in glaucoma simplex

In the study reported here, the relation between the dilatation of the pupil and the course of intracoular pressure (IOP) is examined in open angle glaucoma patients and in glaucoma suspects after topical administration of the combination of guanethidine 3% and adrenaline 0.5% in one eye drop (GA). By treating one eye with GA and leaving the fellow eye untreated on the same day, there was a symmetrical response of IOP, independent of the mydriasis in the treated eyes. It leads to the conclusion that the mydriatic response has no influence on the course of IOP. The physiological explanation for the symmetrical course of IOP in both treated and untreated fellow eyes seems to be a mediation by the bloodstream of GA to the eye which was left untreated.

Verification of the Biphasic Response in Intraocular Pressure During Treatment of Glaucoma Patients With 3% Guanethidine and 0.5% Adrenaline

In a long-term study with 3% guanethidine and 0.5% adrenaline in one eye drop (GA) the combined results of patients with primary open angle glaucoma (POAG) and glaucoma suspects showed a biphasic response in intraocular pressure (IOP). The hypertensive phase peaked 3 hrs after administration (at noon) and reached a maximum of 3.5 mm Hg (p < 0.005) above the hypotensive phase. It is reported in the literature that during office hours untreated glaucoma patients show a peak near noon, suggesting that the initial increase in IOP may be the normal IOP pattern.