Effects of Prostaglandin E₂, F_2α, and Latanoprost Acid on Isolated Ocular Blood Vessels In Vitro

Abstract

The vascular effects of PGE2, PGF2alpha and latanoprost acid on isolated bovine long posterior ciliary arteries and episcleral veins have been investigated using a small vessel myograph. PGE2 caused vasorelaxation both in the ciliary artery and episcleral vein (EC50: 7.9x10(-9) M and 2.1x10(-8) M respectively). Blockade of thromboxane receptors with GR 32191B, a TP receptor antagonist, shifted the concentration-response curves to the left in both preparations, probably indicating a slight co-stimulation of TP receptors in these vessels. Blockade of tachykinin NK-1 receptors had no effect on the PGE2 concentration-response curve. PGF2alpha caused a concentration dependent contraction in half of the ciliary arteries examined and relaxation in the other half. In the presence of the thromboxane receptor antagonist (GR 3211B) PGF2alpha always induced relaxation of the ciliary artery (EC50:1.3x10[-5] M). At higher concentrations PGF2alpha tended to slightly constrict the episcleral veins, but in the presence of the TP receptor antagonist (GR 32191B) only relaxation was observed. Latanoprost acid contracted the ciliary artery at concentrations above 10(-6) M. This effect was completely abolished by the TP receptor antagonist (GR 32191B). In the episcleral vein latanoprost acid induced a slight relaxation but in the presence of the TP receptor antagonist (GR 32191B) no effect was observed. These results indicate that PGE2 invariably induces vasorelaxation of bovine ciliary arteries and episcleral veins, whereas both PGF2alpha and latanoprost acid at high concentrations can cause vasoconstriction probably by stimulating TP receptors. PGF2alpha causes marked relaxation of both ciliary arteries and episcleral veins in the presence of the TP blocker which seems unlikely to be mediated by FP receptors.

Vascular Activities of Prostaglandins and Selective Prostanoid Receptor Agonists in Human Retinal Microvessels

“…Since the stimulation of EP 1 -prostanoid receptors results in intracellular calcium mobilization (Funk et al, 1993;Watabe et al, 1993;Coleman et al, 1994), these receptors may be involved in the mediation of endothelial and smooth muscle cell effects. There is also a recent claim that PGE 2 induces relaxation in isolated bovine long posterior ciliary arteries and episcleral veins, this activity attributed to stimulation of EP-receptors (Astin, 1998). Relaxation could result from the stimulation of EP 2 -and EP 4 -receptor subtypes, but no selective agents were employed in that investigation.…”

“…The vascular effects of PGF 2a appear to be much more complex than those of PGE 2 , the former exhibiting dual dose-related actions in a number of in vitro vascular preparations, including primate cerebral arteries, canine arteries from different organs, the bovine long posterior artery and the bovine retinal artery (Hayashi et al, 1985;Toda et al, 1988;Coleman et al, 1990Coleman et al, , 1994Nielsen and Nyborg, 1990;Kawai and Ohhashi, 1994;Astin, 1998). Higher doses of PGF 2a generally result in vasoconstriction and low doses produce vasorelaxation.…”

“…Prostanoids are known to exert effects on vascular components Giles and Leff, 1988;Coleman et al, 1990;Chen et al, 1995), and some endogenous PGs have been shown to alter regional ocular blood¯ow and exhibit signi®cant vasoactive properties in isolated ophthalmic, ciliary and retinal arteries and veins Nyborg, 1989, 1990;Kulkarni, 1995;Astin, 1998). In glaucomatous eyes, therapies that negatively impact ocular blood¯ow could interfere with the effective transport of oxygen and nutrients to already compromised areas of the retina.…”

Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery

“…Exogenously applied PGF 2a evokes contractions in the ciliary circulation in many species (eg porcine, bovine, canine, lupine vessels [29][30][31] ). Its ability to produce stable, repeatable contractions on repeated exposure makes it useful in the investigation of vascular reactivity.…”

“…It has been shown to cause contraction by stimulating TP prostanoid receptors in bovine long posterior ciliary arteries. 29 It can also cause relaxation by stimulating EP 2 prostanoid receptors in smooth muscle cells, stimulating FP prostanoid receptors in the endothelium causing release of NO 32,33 and causing the release of endogenous prostaglandins, such as PGE 2 in smooth muscle cells. 34 Thus, the degree of vasoconstriction produced is the result of a balance of vasoconstrictor and vasodilator actions.…”