ADENOSINE RECEPTOR BLOCKADE AND NITRIC-OXIDE SYNTHASE INHIBITION IN THE RETINA - IMPACT UPON POSTISCHEMIC HYPEREMIA AND THE ELECTRORETINOGRAM

We performed this study to determine the effect on ocular blood dow an d the electroretinogram of either nitric oxide synthase (NOS) inhibiti on, adenosine receptor blockade or the combination of both after 1 hr of ocular ischemia, Thirty-seven cats under general anesthesia were su bjected to 1 hr of complete ischemia in one eye by raising the intraoc ular pressure above systolic blood pressure, The other eye in each ani mal served as a non-ischemic control, Arterial blood gas tension, syst emic arterial pressure, body temperature, hematocrit, and anesthetic l evel were controlled in each experiment, Cats were divided into four g roups. Group 1 received normal saline injections [intravenous (i.v.) a nd intravitreal], Group 2 adenosine receptor blockade (0.1 ml of 0.01 M 8-sulfophenyltheophylline intravitreal) and saline i.v., Group 3 NOS inhibition (30 mg/kg I-N-G-nitro-arginine-methyl-ester i.v.) and sali ne intravitreal, and Group 4 intravitreal adenosine receptor blockade and NOS inhibition i.v. A subset of Group 3 received I-arginine to inv estigate the reversibility of NOS inhibition, after the blood flow mea surements were completed. Five minutes after the end of ischemia, bloo d flows in retina and choroid were measured using injections of radioa ctively labeled microspheres, Electroretinographic (ERG) studies were carried out before treatment, before ischemia, during ischemia, and 1, 2, 3, and 4 hr after ischemia ended NOS inhibition significantly redu ced basal blood flow in the choroid, and in the retina when combined w ith adenosine receptor blockade, Adenosine receptor blockade complete attenuated post-ischemic hyperemia in the retina, but retinal hyperemi a reappeared when adenosine receptor blockade and NOS inhibition were combined, Adenosine receptor blockade had no effect on ERG recovery af ter ischemia, NOS inhibition led to a reduction of ERG a-and b-wave am plitudes in control eyes, that could be reversed by l-arginine. Nitric oxide (NO) appears to be a significant factor in the regulation of ba sal blood how in the choroid. Adenosine appears to be a major mediator of retinal hyperemia after 60 min of ischemia, Since NOS inhibition a ppeared to have direct effects on ERG wave amplitudes, short-term ERG studies may be of limited nse in assessing the role of NO in postische mic recovery of the retina, Our observations correlate well with the e merging role of NO as a neurotransmitter in the retina, (C) 1997 Elsev ier Science Ltd.