Abstract
Purpose:
To evaluate the vasomotor responses of exogenous carbon monoxide (CO) and hydrogen sulphide (H2S) on isolated rabbit ophthalmic artery and their interaction with endogenous and exogenous nitric oxide (NO).
Methods:
Ophthalmic artery segments, obtained from albino rabbits, mounted on a wire myograph were challenged with cumulative concentrations of phenylephrine (PE) in the presence or absence of NG-nitro-L-arginine (LNNA) to inhibit production of NO, CO-releasing molecules (CORMs) or the H2S-donor GYY4137. Animals were handled according to the ARVO statement for the use of animals in ophthalmology and vision research.
Results:
The maximal vasoconstriction elicited by PE in ophthalmic arteries reached 20-30% of that induced by KCl but was dramatically increased by incubation with LNNA. GYY4137 significantly raised PE-mediated vasoconstriction and reduced relaxation by sodium nitroprusside (SNP); however, GYY4137 depressed PE-induced contractions in the presence of LNNA. CORMs concentration-dependently inhibited PE-induced constriction but were less effective in LNNA-treated arteries. In vascular tissues GYY4137 reduced cyclic GMP (cGMP) levels in normal and SNP-treated vessels. CORMs increased cGMP but this effect was strongly reduced by LNNA.
Conclusions:
In conclusion both H2S and CO are able to relax isolated ophthalmic artery; however, the effect of H2S is seen only in the absence of endogenous NO and does not involve cGMP generation. In contrast, CO stimulates cGMP in a manner that seems to involve endogenous NO. These findings provided new insights into the complexities of gas interactions suggesting new pharmacological strategy for the treatment of ocular diseases.
Keywords: 617 nitric oxide •
711 second messengers: pharmacology/physiology •
616 neurotransmitters/neurotransmitter systems