Nipradilol induces vasodilation of canine isolated posterior ciliary artery via stimulation of the guanylyl cyclase-cGMP pathway.

We examined the effect of nipradilol on contraction of the posterior ciliary artery induced by high potassium or norepinephrine and on cyclic GMP (cGMP) levels in the posterior ciliary artery of dogs. Nipradilol caused dose-dependent relaxation of KCl-and norepinephrine-induced contractions of posterior ciliary artery. The relaxant effect of nipradilol on norepinephrine-contracted ciliary artery was significantly greater than that on KCl-contracted ciliary artery. In KCl-contracted ciliary artery, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) M) did not alter the relaxant effect of nipradilol, whereas 1H-1,2,4-oxadiazolo-4,3-a-quinoxalin-1-one (ODQ, 10(-6) M) significantly inhibited this effect. Ethacrynic acid at 10(-5) M, sulfasalazine at 10(-4) M and S-decylglutathione at 10(-4) M (glutathione S-transferase inhibitors) did not inhibit the relaxant effect of nipradilol. In addition, nipradilol produced dose-dependent increases in cGMP levels in the canine posterior ciliary artery. These findings indicate that nipradilol-induced vasorelaxation in the canine posterior ciliary artery occurs via stimulation of the guanylyl cyclase-cGMP pathway.

Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery.

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 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