Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits.
OBJECTIVE
Nitric oxide (NO) may control intraocular pressure (IOP)-regulating mechanisms physiologically and in ocular diseases such as glaucoma. The aim of the present study was to clarify whether an increase in aqueous humor outflow facility could explain the IOP-lowering effect of the NO/cyclic GMP pathway we recently described.


METHODS
Test compounds were administered to anesthetized rabbits (New Zealand White, n = 6) intracamerally (5 microl) in the following doses: nitrosocaptopril 12.3 microg, captopril 10.9 microg, sodium nitroprusside (SNP) 13.1 microg and 8-Br-cGMP 22.3 microg. Outflow facility (C) was determined by the two-level constant pressure infusion method. Outflow facility, C( 1) and C(2), was measured at lower and higher pressure levels, respectively.


RESULTS
Outflow facility was increased after treatment with SNP (increase in C in the experimental eye as compared to the control eye C( 1) 80% and C(2) 74%), nitrosocaptopril (C(1) 69% and C(2) 64%) and 8-Br-cGMP (C(1) 35% and C(2) 33%). Captopril had no effect on outflow facility (C(1) -12% and C(2) 2%). Blood pressure was not affected by the drugs.


CONCLUSIONS
We conclude that enhancement of outflow facility by nitrosocaptopril, SNP and 8-Br-cGMP, their second messenger derivative, at least partly explains the IOP-lowering effect of NO releasing compounds.
Kotikoski
Hanna
H
Institute of Biomedicine, Biomedicum Helsinki, Pharmacology, University of Helsinki, Helsinki, Finland.
Vapaatalo
Heikki
H
Oksala
Olli
O
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001082:Aqueous Humor / Q000378:metabolism*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits
C060039:S-nitrosocaptopril; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D002216:Captopril; D006152:Cyclic GMP