ABSTRACT
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on experimental allergic conjunctivitis, induced by ocular challenge with antigen in actively sensitized guinea pigs, were investigated. NSAIDs reduced the increase in prostaglandin D2 (PGD2) and E2 (PGE2) in the ocular lavage fluid. The inhibition of NSAIDs to these increases was approximately 90%-95%. NSAIDs also lowered itch-scratch response (ISR) to approximately one-third to one-half of the vehicle-treated group. However, these drugs scarcely affected plasma exudation in the conjunctiva. Ketotifen, an H1 histamine receptor antagonist, inhibited both pathophysiological changes (inhibition: 70%-80%). However, this drug was less efficacious than NSAIDs in reducing PGD2 and PGE2 levels. Moreover, topical administration of histamine induced ISR and plasma exudation; in contrast, PGD2 induced ISR exclusively. These results suggest that a part of antigen-induced ISR may be attributable to PGs. However, PGs may not play a key role in plasma exudation; other mediators such as histamine may be involved.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Conjunctivitis, Allergic/drug therapy , Disease Models, Animal , Administration, Topical , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antigens/administration & dosage , Antigens/adverse effects , Benzophenones/pharmacokinetics , Benzopyrans/administration & dosage , Benzopyrans/pharmacokinetics , Bromobenzenes/pharmacokinetics , Conjunctivitis, Allergic/etiology , Diclofenac/administration & dosage , Diclofenac/pharmacokinetics , Dinoprostone/antagonists & inhibitors , Dinoprostone/chemistry , Dinoprostone/metabolism , Evans Blue , Exudates and Transudates/chemistry , Eye/drug effects , Guinea Pigs , Histamine/administration & dosage , Histamine/adverse effects , Histamine Release/drug effects , Immunization , Injections, Intraperitoneal , Injections, Subcutaneous , Ketotifen/administration & dosage , Ketotifen/pharmacokinetics , Ketotifen/therapeutic use , Male , Ovalbumin/administration & dosage , Ovalbumin/pharmacology , Propionates/administration & dosage , Propionates/pharmacokinetics , Prostaglandin D2/antagonists & inhibitors , Prostaglandin D2/chemistry , Prostaglandin D2/metabolism , Pruritus/chemically induced , Pruritus/prevention & control , Therapeutic Irrigation/methodsABSTRACT
PURPOSE: To investigate the ocular effect of intravenous administration of a phosphodiesterase type 3 inhibitor (NSP-805) and to compare the effect of NSP-805 with that of a calcium antagonist (nicardipine hydrochloride) on chorio-retinal blood flow in anesthetized albino rabbits. METHODS: Twenty-four female albino rabbits (weighting 2.0-4.0 kg) were anesthetized with intravenous injection. NSP-805(40 micrograms/kg and 100 micrograms/kg) and nicardipine of 40 micrograms/kg were intravenously administrated to the anesthetized rabbits. Intravenously administration of 20% dimethyl sulfoxide (DMSO) was used as a vehicle. Chorio-retinal blood flow was measured with a laser Doppler flowmeter at baseline and every 20 minutes after intravenous administration for 120 minutes. Heart rates and systemic blood pressure were monitored. Baseline measurements were compared with every 10 minutes after intravenous administration. Differences between the drug groups and vehicle group were analyzed. RESULTS: After administration of a low dose of NSP--805 (40 micrograms/kg) and nicardipine (40 micrograms/kg), the chorio-retinal blood flow was significantly increased (p < 0.05). A high dose NSP-805(100 micrograms/kg) reduced systemic blood pressure significantly, but the increase of chorio-retinal blood flow was less than that at the low dose of NSP-805(40 micrograms/kg) and nicardipine (40 micrograms/kg). Chorio-retinal blood flow in the NSP 805(40 micrograms/kg) and nicardipine (40 micrograms/kg) groups was significantly increased over that in the control group (20% DMSO) (p < 0.05). CONCLUSION: The results suggest that the NSP-805 has the potential of increasing chorio-retinal blood flow in rabbit eyes.
