A study on the vascular effects of prostaglandin F2α[ and latanaprost in the eye with special reference to the surface hyperaemia after topical administration

Abstract: The ocular hypotensive effect of topically applied prostaglandins is usually accompanied byconjunctival hyperaemia and irritation. The purpose of the present study was to investigate thepharmacological mechanism of the ocular surface hyperaemia induced by topically appliedprostaglandins, particularly prostaglandin F2α (PGF2α) and its synthetic analogue latanoprost, aselective FP prostanoid receptor agonist.The hyperaemia 1 hour after topical application of 1 µg PGF2α-isopropyl ester (PGF2α-ie) wasaccompanied by a marked increase of substance P-like immunoreactivity (SP-LI) and CGRP-likeimmunoreactivity (CGRP-LI) in the aqueous humor (studied by radioimmunoassay), and significantincrease in blood flow to the surface structures and the anterior uvea (determined with radioactivelylabelled microspheres). The increase in blood flow was blocked by nitric oxide (NO) synthaseinhibition with L-NMMA, and by sensory denervation, particularly in the surface structures.Latanoprost caused clearly less hyperaemia than PGF2α-ie. The visible hyperaemic response to latanoprost at a dose of 10 µg was not associated with an increase in the blood flow or with SP-LI and CGRP-LI release into the aqueous humor. This prompted an investigation of the effects of the prostaglandins on veins.In vitro the vascular effect was studied by using a small vessel myograph. PGF2α caused relaxation of both bovine episcleral veins and long posterior ciliary arteries, in presence of GR32191B, a thromboxane (TP) receptor antagonist. The effects of latanoprost acid were negligible. Both PGF2α, and latanoprost acid induced relaxation of rabbit submental vein in presence of GR32191B. These effects were totally abolished by NO synthase inhibition with L-NAME and by denuding the endothelium, and significantly attenuated by blocking NK-1 and CGRP receptors with GR 82334 and CGRP 8-37, respectively.These results suggest that PGF2α-ie causes surface hyperaemia in rabbit eye by dilating arteries and veins, an effect mediated primarily by NO. The increased blood flow was furthermore caused by stimulation of sensory nerves. As latanoprost had no effect on blood flow, but did dilate veins, it would appear that the relaxation of the veins, but not the arteries; was mediated by FP receptors. Furthermore, both substance P and CGRP seem to be involved in the vasodilation induced by both prostaglandins.