Atropine‐mydriasis NO‐system Dependent, L‐NAME‐miosis, L‐arginine‐miosis, and Counteraction by Stable Gastric Pentadecapeptide BPC 157, in Living Rats

In living rats, atropine‐mydriasis would depend on NO‐related mechanisms in a particular way: both L‐NAME, a NOS‐blocker and L‐arginine, a NOS‐substrate wouldexhibit a miotic effect, not yet described; the atropine‐mydriasis and L‐NAME‐ and L‐arginine‐miosis, could consequently be counteracted by BPC 157 due to its interactions with the NO‐system and sphincter function. We administraded BPC 157 (10µg, 10ng, 10pg/kg), L‐NAME (5mg/kg), and/or L‐arginine (100mg/kg) alone/together intraperitoneally in healthy rats (miosis‐studies) or at 30 min after 1% atropine/2drops/eye (mydriasis‐studies). BPC 157 does not alter normal pupil diameter while miosis occured promptly after both L‐NAME and L‐arginine, lasting for more than 3h, when they were given alone. When L‐NAME+L‐arginine were given together, this miosis was shorter, suggesting that their separate miotic effects are competitive and may antagonize each other. These L‐NAME‐/L‐arginine‐effects were both shortened in rats that received BPC 157. In case of maximal atropine‐mydriasis all of the agents, BPC 157, L‐NAME and L‐arginine, induce a counteraction, commencing sooner in BPC 157‐rats, but all of the agents lead to completely blunted atropine‐mydriasis returning to regular pupil size hours sooner than in atropine‐rats which received saline. Concluding, BPC 157 may counteracted those effects due to its interactions with the NO‐system and sphincter function. Supported by Grant 108‐1083570‐3635, Croatia.