In:
Journal of Vascular Research, S. Karger AG, Vol. 35, No. 4 ( 1998), p. 285-294
Abstract:
In the guinea pig basilar artery, acetylcholine and the calcium ionophore A23187 induced endothelium-dependent relaxations, which were not significantly affected by the nitric oxide (NO) synthase inhibitor N 〈 sup 〉 ω 〈 /sup 〉 -nitro- 〈 i 〉 L 〈 /i 〉 -arginine ( 〈 i 〉 L 〈 /i 〉 -NOARG; 0.3 m 〈 i 〉 M 〈 /i 〉 ) or the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a] quinoxaline-1-one; 1-10 µ 〈 i 〉 M 〈 /i 〉 ), or by these inhibitors combined. However, acetylcholine (10 µ 〈 i 〉 M 〈 /i 〉 ) and A23187 (3 µ 〈 i 〉 M 〈 /i 〉 ) each significantly increased the tissue level of cGMP in the absence but not in the presence of 〈 i 〉 L 〈 /i 〉 -NOARG, suggesting that NO is released from the vascular endothelium in this blood vessel. Treatment with the potassium (K) channel inhibitors charybdotoxin (0.1 µ 〈 i 〉 M 〈 /i 〉 ) plus apamin (0.1 µ 〈 i 〉 M 〈 /i 〉 ), a toxin mixture previously shown to inhibit relaxations mediated by endothelium-derived hyperpolarizing factor (EDHF) in this artery, had no effect on the A23187-induced relaxation but slightly inhibited the response to acetylcholine (E 〈 sub 〉 max 〈 /sub 〉 was reduced by 24%). When the action of EDHF was prevented by these K channel inhibitors, the remaining relaxation was abolished by either ODQ (1 µ 〈 i 〉 M 〈 /i 〉 ) or 〈 i 〉 L 〈 /i 〉 -NOARG (0.3 m 〈 i 〉 M 〈 /i 〉 ), indicating that NO, apart from EDHF, contributes to the endothelium-dependent relaxations. Furthermore, ODQ (10 µ 〈 i 〉 M 〈 /i 〉 ) abolished the relaxation induced by the NO donor S-nitroso-N-acetylpenicillamine. Thus, activation of soluble guanylate cyclase seems to be the only mechanism through which NO causes relaxation in this artery. When vessels were exposed to grave hypoxia (pO 〈 sub 〉 2 〈 /sub 〉 = 6 mm Hg), the NO-mediated relaxation (induced by acetylcholine in the presence of charybdotoxin plus apamin) disappeared. In contrast, EDHF-mediated responses (elicited by acetylcholine in the presence of 〈 i 〉 L 〈 /i 〉 -NOARG) were only marginally affected by hypoxia (E 〈 sub 〉 max 〈 /sub 〉 was reduced by 16%). 17-Octadecynoic acid (50 µ 〈 i 〉 M 〈 /i 〉 ) and 5,8,11,14-eicosatetraynoic acid (10 µ 〈 i 〉 M 〈 /i 〉 ), inhibitors of cytochrome P 〈 sub 〉 450 〈 /sub 〉 -dependent oxidation of arachidonic acid, failed to inhibit the acetylcholine-induced relaxation in the presence of 〈 i 〉 L 〈 /i 〉 -NOARG. The cytochrome P 〈 sub 〉 450 〈 /sub 〉 -dependent arachidonic acid metabolite 11,12-epoxyecosatrienoic acid (0.3–3.0 µ 〈 i 〉 M 〈 /i 〉 ) had no relaxant effect per se. In conclusion, EDHF and NO are both mediators of endothelium-dependent relaxations in the guinea pig basilar artery. However, during grave hypoxia, EDHF alone mediates acetylcholine-induced relaxation. The results further suggest that EDHF is not a metabolite of arachidonic acid formed by cytochrome P 〈 sub 〉 450 〈 /sub 〉 mono-oxygenase or generated by another oxygen-dependent enzyme in this artery.
Type of Medium:
Online Resource
ISSN:
1018-1172
,
1423-0135
Language:
English
Publisher:
S. Karger AG
Publication Date:
1998
detail.hit.zdb_id:
1482726-8
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