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The Nitroxyl Anion (HNO) Is A Potent Dilator Of Rat Coronary Vasculature.

J. Favaloro, B. Kemp-Harper
Published 2007 · Chemistry, Medicine

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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. METHODS Sprague-Dawley rat hearts were retrogradely perfused with Krebs' solution (8 ml/min) using the Langendorff technique. Perfusion pressure was raised using a combination of infusion of phenylephrine and bolus additions of the thromboxane mimetic U46619 to attain a baseline perfusion pressure of 100-120 mm Hg. The vasodilator effects of a nitroxyl anion donor, Angeli's salt, were examined in the absence and presence of HNO and NO* scavengers, K+ channel inhibition, and soluble guanylate cyclase (sGC) inhibition. In addition, the inotropic and chronotropic effects of Angeli's salt were examined in hearts at resting perfusion pressure (50-60 mm Hg) and compared to responses evoked by acetylcholine and isoprenaline. RESULTS Angeli's salt causes a potent and reproducible vasodilatation in isolated perfused rat hearts. This response is unaffected by the NO* scavenger hydroxocobalamin (0.1 mM) but is significantly inhibited by the HNO scavenger N-acetyl-L-cysteine (4 mM), suggesting that HNO is the mediator of the observed responses. Vasodilatation responses to Angeli's salt were virtually abolished in the presence of the sGC inhibitor ODQ (10 microM). The magnitude of the vasodilatation response to Angeli's salt was significantly reduced in the presence of 30 mM K+, 10 microM glibenclamide and in the presence of the calcitonin gene-related peptide (CGRP) antagonist CGRP((8-37)) (0.1 microM). Angeli's salt had little effect on heart rate or force of contraction, whilst isoprenaline and acetylcholine elicited significant positive and negative cardiotropic effects, respectively. CONCLUSIONS The HNO donor Angeli's salt elicits a potent and reproducible vasodilatation response. The results suggest that the response is elicited by HNO through sGC-mediated CGRP release and K(ATP) channel activation.
This paper references
Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion
J. Wanstall (2001)
A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system
K. Miranda (2003)
Nitroxyl gets to the heart of the matter
M. Feelisch (2003)
NO‐ Activates Soluble Guanylate Cyclase and Kv Channels to Vasodilate Resistance Arteries
J. Irvine (2003)
Potassium channels in the coronary circulation
M. Gollasch (2001)
Regional localization and abundance of calcitonin gene-related peptide receptors in guinea pig heart.
Y. Chang (2001)
Hydrogen peroxide-supported oxidation of NG-hydroxy-L-arginine by nitric oxide synthase.
R. A. Pufahl (1995)
Regulation of potassium channels in coronary arterial smooth muscle by endothelium-derived vasodilators.
P. Li (1997)
Comparison of responses to novel nitric oxide donors in the feline pulmonary vascular bed.
B. D. De Witt (2001)
No {middle dot}NO from NO synthase
H. Schmidt (1996)
Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins. A chemical discussion of the differential biological effects of these redox related products of NOS.
K. Miranda (2003)
No .NO from NO synthase.
H. Schmidt (1996)
Conversion of nitroxyl (HNO) to nitric oxide (NO) in biological systems: the role of physiological oxidants and relevance to the biological activity of HNO.
J. Fukuto (1993)
Sodium azide dilates coronary arterioles via activation of inward rectifier K+ channels and Na+-K+-ATPase.
E. Qamirani (2006)
Ischemic preconditioning changes the pattern of coronary reactive hyperemia regardless of mitochondrial ATP-sensitive K(+) channel blockade.
P. Pagliaro (2002)
Nitrergic relaxation in urethral smooth muscle: involvement of potassium channels and alternative redox forms of NO
G. Costa (2001)
Calcitonin gene-related peptide in the cardiovascular system: characterization of receptor populations and their (patho)physiological significance.
D. Bell (1996)
Orthogonal properties of the redox siblings nitroxyl and nitric oxide in the cardiovascular system: a novel redox paradigm.
D. Wink (2003)
Nitric oxide (NO), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase.
E. A. Dierks (1996)
Comparison of the redox forms of nitrogen monoxide with the nitrergic transmitter in the rat anococcygeus muscle
C. G. Li (1999)
Reactions of nitric oxide with mitochondrial cytochrome c: a novel mechanism for the formation of nitroxyl anion and peroxynitrite.
M. Sharpe (1998)
K. Dellsperger (1996)
On the acidity and reactivity of HNO in aqueous solution and biological systems
M. D. Bartberger (2001)
Differential actions of L‐cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta
A. Ellis (2000)
Role of copper ions and cytochrome P450 in the vasodilator actions of the nitroxyl anion generator, Angeli's salt, on rat aorta.
S. Nelli (2001)
Oxidation of nitroxyl anion to nitric oxide by copper ions
S. Nelli (2000)
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
S. Brain (2004)
The cardioprotective effects of nitroglycerin-induced preconditioning are mediated by calcitonin gene-related peptide.
C. Hu (1999)
NO+, NO, and NO- donation by S-nitrosothiols: implications for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation.
D. Arnelle (1995)
Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury.
X. Ma (1999)
Positive inotropic and lusitropic effects of HNO/NO− in failing hearts: Independence from β-adrenergic signaling
N. Paolocci (2003)
Bioassay discrimination between nitric oxide (NO.) and nitroxyl (NO-) using L-cysteine.
R. Pino (1994)
Formation of free nitric oxide from l-arginine by nitric oxide synthase: direct enhancement of generation by superoxide dismutase.
A. Hobbs (1994)
Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels
M. Nelson (1990)
Arginine Conversion to Nitroxide by Tetrahydrobiopterin-free Neuronal Nitric-oxide Synthase
S. Adak (2000)
Calcitonin gene-related peptide-dependent vascular relaxation of rat aorta. An additional mechanism for nitroglycerin.
B. Booth (2000)
The Langendorff heart preparation—Reappraisal of its role as a research and teaching model for coronary vasoactive drugs
K. Broadley (1979)
Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling
N. Paolocci (2001)

This paper is referenced by
Ring expansions of acyloxy nitroso compounds.
M. Hadimani (2015)
Comparison of Reductive Ligation‐Based Detection Strategies for Nitroxyl (HNO) and S‐Nitrosothiols
Zhengrui Miao (2016)
Acyloxy nitroso compounds as nitroxyl (HNO) donors: kinetics, reactions with thiols, and vasodilation properties.
Mai E. Shoman (2011)
Nitrite- and nitroxyl-induced relaxation in porcine coronary (micro-) arteries: underlying mechanisms and role as endothelium-derived hyperpolarizing factor(s).
Ilse P.G. Botden (2012)
Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle
Mirko Gastreich-Seelig (2020)
Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy: NO* and beyond.
R. Ritchie (2009)
The trans effect of nitroxyl (HNO) in ferrous heme systems: implications for soluble guanylate cyclase activation by HNO.
L. Goodrich (2013)
Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl–l-Cysteine-Sensitive Factor(s)
S. Kagota (2018)
Nitroxyl Activates SERCA in Cardiac Myocytes via Glutathiolation of Cysteine 674
Steve Lancel (2009)
A selective phosphine-based fluorescent probe for nitroxyl in living cells.
Zhengrui Miao (2015)
The nitric oxide-iron interplay in mammalian cells: transport and storage of dinitrosyl iron complexes.
D. Richardson (2008)
Pharmacological Characterization of 1-Nitrosocyclohexyl Acetate, a Long-Acting Nitroxyl Donor That Shows Vasorelaxant and Antiaggregatory Effects
Sonia Donzelli (2013)
The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles
Bernd Mayer (2008)
The concomitant coronary vasodilator and positive inotropic actions of the nitroxyl donor Angeli's salt in the intact rat heart: contribution of soluble guanylyl cyclase‐dependent and ‐independent mechanisms
K. Y. Chin (2014)
A near-infrared fluorescent probe for the selective detection of HNO in living cells and in vivo.
P. Liu (2015)
Calcitonin gene-related peptide: physiology and pathophysiology.
F. A. Russell (2014)
Nitroglycerine and sodium trioxodinitrate: from the discovery to the preconditioning effect.
P. Pagliaro (2013)
Effect of Angeli’s salt on the glutamate/glutamine cycle activity and on glutamate excitotoxicity in the hamster retina
M. Knott (2012)
A Near-Infrared Fluorescent Probe for Detection of Nitroxyl in Living Cells
P. Liu (2015)
Increased adrenomedullin protein content and mRNA expression in human fetal membranes but not placental tissue in pre-eclampsia.
A. Al-Ghafra (2006)
In vivo effects of nitrosyl hydrogen on cardiac function and sarcoplasmic reticulum calcium pump (SERCA2a) in rats with heart failure after myocardial infarction.
Yanqing Guo (2020)
Mechanisms underlying the endothelium-dependent modulation of vascular tone
P. L. Iarova (2011)
HNO–Thiol Relationship
M. Filipovic (2017)
The opposing roles of NO and oxidative stress in cardiovascular disease.
R. Ritchie (2017)
HNO/Thiol Biology as a Therapeutic Target
J. Miljkovic (2016)
Novel primary amine diazeniumdiolates—Chemical and biological characterization
M. Puglisi (2018)
Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses.
B. Wynne (2012)
Chronic administration of the HNO donor Angeli's salt does not lead to tolerance, cross-tolerance, or endothelial dysfunction: comparison with GTN and DEA/NO.
J. Irvine (2011)
The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats
Ana C Zarpelon (2013)
The Anti-fibrotic Actions of Relaxin Are Mediated Through a NO-sGC-cGMP-Dependent Pathway in Renal Myofibroblasts In Vitro and Enhanced by the NO Donor, Diethylamine NONOate
C. Wang (2016)
Gender specific generation of nitroxyl (HNO) from rat endothelium.
K. Hamilton (2015)
Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.
C. G. Tocchetti (2011)
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