Does prostacyclin mediate alpha-adrenergic induced hypotension?

Area of Science:

• Ophthalmology
• Pharmacology
• Biochemistry

Background:

• Tranylcypromine (TCP) affects intraocular pressure (IOP) after topical catecholamine administration.
• Previous studies noted TCP's influence on IOP, but the mechanism was unclear.

Purpose of the Study:

• To investigate the mechanism by which TCP inhibits the hypotensive phase following topical norepinephrine (nE) and epinephrine (E) administration.
• To determine if this effect is related to monoamine oxidase (MAO) inhibition, alpha-receptor blockade, or prostacyclin synthesis.

Main Methods:

• Topical administration of TCP, nE, E, and isoproterenol in normal and chemically denervated rabbit eyes.
• Assessment of TCP's effect on alpha-adrenergic induced hypotension using phenoxybenzamine (PBA), timolol maleate, and indomethacin.
• Measurement of prostacyclin-like activity via bioassay using rat platelet aggregation.

Main Results:

• TCP inhibited the hypotensive phase after topical nE and E in normal eyes, an effect enhanced in denervated eyes.
• Phenoxybenzamine blocked TCP's effect on alpha-adrenergic hypotension, but timolol and indomethacin did not.
• TCP reduced prostacyclin-like activity in aqueous and iris, while topical nE increased it in aqueous humor.

Conclusions:

• The inhibitory effect of TCP on the hypotensive phase of topical E and nE is primarily due to the inhibition of prostacyclin synthesis.
• This effect is independent of MAO inhibition or alpha-receptor blockade.
• Prostacyclin produced by the iris and ciliary body may maintain lower basal IOP levels.