Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance

Karen L Andrews; Natalie G Lumsden; Julie Farry; Ann-Maree Jefferis; Barbara K Kemp-Harper; Jaye P F Chin-Dusting

doi:10.1042/CS20140759

Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance

Karen L Andrews, Natalie G Lumsden, Julie Farry, Ann-Maree Jefferis, Barbara K Kemp-Harper, Jaye P F Chin-Dusting

Pharmacology

Research output: Contribution to journal › Article › Research › peer-review

31 Citations (Scopus)

Abstract

Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO*), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and saphenous veins were obtained from patients undergoing coronary artery graft surgery and mounted in organ baths. Repeated vasodilator responses to the HNO donor Angeli s salt (AS) and NO* donor glyceryl trinitrate (GTN) were determined. AS- and GTN-induced concentration-dependent vasorelaxation of both human radial arteries (AS pEC50: 6.5+/-0.2; -log M) and saphenous veins (pEC50: 6.7+/-0.1) with similar potency. In human radial arteries, GTN-induced relaxation was reduced by the NO* scavenger hydroxocobalamin (HXC; P

Original language	English
Pages (from-to)	179 - 187
Number of pages	9
Journal	Clinical Science
Volume	129
Issue number	2
DOIs	https://doi.org/10.1042/CS20140759
Publication status	Published - 2015

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abstract = "Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO*), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and saphenous veins were obtained from patients undergoing coronary artery graft surgery and mounted in organ baths. Repeated vasodilator responses to the HNO donor Angeli s salt (AS) and NO* donor glyceryl trinitrate (GTN) were determined. AS- and GTN-induced concentration-dependent vasorelaxation of both human radial arteries (AS pEC50: 6.5+/-0.2; -log M) and saphenous veins (pEC50: 6.7+/-0.1) with similar potency. In human radial arteries, GTN-induced relaxation was reduced by the NO* scavenger hydroxocobalamin (HXC; P",

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AU - Lumsden, Natalie G

AU - Farry, Julie

AU - Jefferis, Ann-Maree

AU - Kemp-Harper, Barbara K

AU - Chin-Dusting, Jaye P F

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Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance

Abstract

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