A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries.

Background And Purpose: Nitroxyl (HNO) is emerging as an important regulator of vascular tone as it is potentially produced endogenously and dilates conduit and resistance arteries. This study investigates the contribution of endogenous HNO to endothelium-dependent relaxation and hyperpolarization in resistance arteries.

Experimental Approach: Rat and mouse mesenteric arteries were mounted in small vessel myographs for isometric force and smooth muscle membrane potential recording.

Redox variants of NO (NO{middle dot} and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms.

The free radical form of nitric oxide (NO(.)) is a well-known mediator of vascular tone. What is not so well recognized is that NO(.

Nitroxyl (HNO): the Cinderella of the nitric oxide story.

Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic advantages over its redox sibling, NO*. Thus, unlike NO*, HNO can target cardiac sarcoplasmic ryanodine receptors to increase myocardial contractility, can interact directly with thiols and is resistant to both scavenging by superoxide (*O2-) and tolerance development.

Nitroxyl anion donor, Angeli's salt, does not develop tolerance in rat isolated aortae.

The nitroxyl anion (HNO) is emerging as a novel regulator of cardiovascular function with therapeutic potential in the treatment of diseases such as heart failure. It remains unknown whether tolerance develops to HNO donors, a limitation of currently used nitrovasodilators. The susceptibility of the HNO donor, Angeli's salt (AS), to the development of vascular tolerance was compared with the NO donors, glyceryl trinitrate (GTN) and diethylamine/NONOate (DEA/NO) in rat isolated aortae.

The nitroxyl anion (HNO) is a potent dilator of rat coronary vasculature.

Objective: The nitroxyl anion (HNO) is the one-electron reduction product of NO(). This redox variant has been shown to be endogenously produced and to have effects that are pharmacologically distinct from NO(). This study investigates the vasodilator and chronotropic effects of HNO in the rat isolated coronary vasculature.

Vasorelaxation and hyperpolarisation of rat small mesenteric artery by the quaternary anion tetraphenylboron.

This study characterises the vasorelaxation and hyperpolarisation effects of the negatively charged quaternary compound tetraphenylboron (TPB) in the rat small mesenteric artery. Segments of rat small mesenteric artery were mounted in a myograph and vessel tone and membrane potential were measured simultaneously. In vessels pre-contracted with vasopressin (0.

NO- activates soluble guanylate cyclase and Kv channels to vasodilate resistance arteries.

Nitric oxide (NO) plays an important role in the control of vascular tone. Traditionally, its vasorelaxant activity has been attributed to the free radical form of NO (NO*), yet the reduced form of NO (NO-) is also produced endogenously and is a potent vasodilator of large conduit arteries. The effects of NO- in the resistance vasculature remain unknown.

Novel imidazoline compounds that inhibit Kir-mediated vasorelaxation in rat middle cerebral artery.

The ability of a series of novel imidazoline (IMID) compounds (fluoryl-, methoxy- and methyl-phenyl derivatives of clonidine) to inhibit the vasorelaxation and hyperpolarisation response to exogenous K+ (1-10 mM) was assessed in the rat middle cerebral artery (MCA) using the small vessel myograph. In this preparation, K+ -induced relaxation was inhibited by low concentrations of Ba2+ (30 microM) but not affected by the Na+/K+ ATPase inhibitor ouabain (10 microM), or a combination of tetraethylammonium (TEA; 1 mM), 4-aminopyridine (1 mM) and glibenclamide (10 microM). These results are consistent with K+ eliciting a vasorelaxation response through the activation of inwardly rectifying K+ channels (Kir channels) in this tissue.