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Claudio Bucolo, Roberta Foresti, Giovanni Giurdanella, Filippo Drago, Salvatore Salomone; INTERACTIONS OF GASEOUS NEUROMODULATORS IN THE CONTROL OF RABBIT OPHTHALMIC VASCULAR TONE. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4357.
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© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
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.
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