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Differential effects of ouabain on the vasodilator actions of nitric oxide and S-nitrosothiols in vivo: relevance to the identity of EDRF/EDHF.

Abstract：

OBJECTIVES:This study examined the role of Na+/K+-ATPase in the vasodilator actions of nitric oxide (NO), S-nitrosothiols and the endothelium-dependent agonist, acetylcholine. METHODS:The vasodilator responses elicited by intravenous injections of (i) the NO-donors, sodium nitroprusside and MAHMA NONOate, (ii) the S-nitrosothiols, L-S-nitrosocysteine and S-nitrosocoenzyme A, and (iii) acetylcholine, in urethane-anesthetized rats. RESULTS:The NO-donors, S-nitrosothiols and acetylcholine elicited dose-dependent depressor responses and reductions in hindquarter (HQR) and mesenteric (MR) vascular resistances. The depressor responses and associated reductions in HQR elicited by NO-donors were markedly attenuated after injection of ouabain. In contrast, the depressor responses and reductions in HQR elicited by the S-nitrosothiols and acetylcholine were not affected. The reductions in MR elicited by all vasodilator agents were exaggerated after injection of ouabain. Finally, the decomposition of sodium nitroprusside, MAHMA NONOate, L-S-nitrosocysteine and S-nitrosocoenzyme A to NO upon addition to rat blood or vascular preparations was not affected by ouabain. CONCLUSION:This study demonstrates that ouabain has opposing effects on NO-mediated vasodilation in resistance arteries in the hindquarter and mesenteric beds of the rat. The similarity of effects of ouabain on the vasodilator actions of acetylcholine, L-S-nitrosocysteine and S-nitrosocoenzyme A as opposed to the NO-donors supports the possibility that endothelium-derived relaxing factor released by acetylcholine in resistance arteries is an S-nitrosothiol.

journal_name

Vascul Pharmacol

journal_title

Vascular pharmacology

authors

Lewis SJ,Travis MD,Hashmi-Hill MP,Sandock K,Robertson TP,Bates JN

doi

10.1016/j.vph.2006.06.008

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

383-94

issue

6

eissn

1537-1891

issn

1879-3649

pii

S1537-1891(06)00123-6

journal_volume

45

pub_type

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