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Vascul Pharmacol. 2006 Dec;45(6):383-94. Epub 2006 Jun 17.

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

Author information

1
Department of Physiology and Pharmacology, University of Georgia, Athens, GA, USA. slewis@vet.uga.edu

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.

PMID:
16861050
DOI:
10.1016/j.vph.2006.06.008
[Indexed for MEDLINE]

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