Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery.
OBJECTIVE
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 F(2alpha): 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. Eye (2003) 17, 628-636. doi:10.1038/sj.eye.6700437
Quinn
S
S
Department of Human Anatomy and Physiology, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Ireland.
O'Brien
C
C
McLoughlin
P
P
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism; D019842:Ciliary Arteries / Q000187:drug effects / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D009569:Nitric Oxide; D002248:Carbon Monoxide; D011464:Epoprostenol; D006419:Heme Oxygenase (Decyclizing); D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester