Abstract
Purpose Vascular endothelial cell dysfunction has been noted in patients with normal pressure glaucoma. Although nitric oxide (NO) accounts for a large proportion of vasorelaxation in the posterior ciliary artery, considerable relaxation remains unexplained. We investigated the roles of haemoxygenase (HO) and cyclooxygenase (COX), which produce the vasodilators carbon monoxide (CO) and prostacyclin, respectively, in NO-independent endothelium-dependent vasodilatation in porcine posterior ciliary arteries.
Methods Isolated vascular rings were mounted in a Mulvaney-Halpern small vessel myograph for the measurement of isometric tension development. Vasodilator responses to bradykinin (BK) were elicited in each ring on three separate occasions following preconstriction with prostaglandin F2α: first in the absence of inhibitors, second in the presence of the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 10−3 M), and third in the presence of L-NAME and either a COX (indomethacin, 10−6 M) or an HO inhibitor (tin protoporphyrin-IX 10−5 M). Results were expressed as a percentage of the maximal relaxation in the presence of L-NAME alone.
Results Incubation with indomethacin (n=6), in the presence of L-NAME, significantly reduced (P<0.01) maximum BK-induced relaxation (−103.5±8.8%) compared to paired rings in the presence of L-NAME alone (−130.8±8.8%). HO inhibition did not reduce NO-independent, BK-induced relaxation when compared to paired control vessels.
Conclusions These data suggest that in the presence of L-NAME, a COX product accounts for a significant proportion of NO-independent vasodilatation. In contrast, endogenous CO production does not have a functionally significant role in the porcine ciliary artery.
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Supported by the Health Research Board, Ireland
Part of this work was presented at EVER meeting in Palma, Majorca, September 1999 and at the Annual Meeting of The Glaucoma Society (Britain and Éire) in London, November, 1999.
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Quinn, S., O'Brien, C. & McLoughlin, P. Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery. Eye 17, 628–636 (2003). https://doi.org/10.1038/sj.eye.6700437
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DOI: https://doi.org/10.1038/sj.eye.6700437
