Effects of nitric oxide donors on cardiac contractility in wild‐type and myoglobin‐deficient mice

The effects of the nitric oxide (NO) donors S‐nitroso‐N‐acetylpenicillamine (SNAP), sodium(Z)‐1‐(N,N‐diethylamino)diazen‐1‐ium‐1,2‐diolate (DEA‐NONOate), and (Z)‐1‐[N‐(2‐Aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA‐NONOate) on force of contraction (Fc) were studied in atrial an...

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Published in:British journal of pharmacology 2002-06, Vol.136 (3), p.415-420
Main Authors: Wegener, J W, Gödecke, A, Schrader, J, Nawrath, H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Electric Stimulation
Enzyme Inhibitors - pharmacology
Female
force of contraction
Fundamental and applied biological sciences. Psychology
guanylyl cyclase
Heart
heart muscle
Hydrazines - pharmacology
In Vitro Techniques
Male
Mice
Myocardial Contraction - drug effects
Myocardium - enzymology
myoglobin
Myoglobin - deficiency
Myoglobin - genetics
Nitric oxide
Nitric Oxide Donors - pharmacology
Nitrogen Oxides
Nitroso Compounds
Oxadiazoles - pharmacology
Quinoxalines - pharmacology
S-Nitroso-N-Acetylpenicillamine - pharmacology
Vertebrates: cardiovascular system
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Summary:The effects of the nitric oxide (NO) donors S‐nitroso‐N‐acetylpenicillamine (SNAP), sodium(Z)‐1‐(N,N‐diethylamino)diazen‐1‐ium‐1,2‐diolate (DEA‐NONOate), and (Z)‐1‐[N‐(2‐Aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA‐NONOate) on force of contraction (Fc) were studied in atrial and ventricular muscle strips obtained from wild‐type (WT) and myoglobin‐deficient (myo−/−) mice. SNAP slightly reduced Fc in preparations from WT mice at concentrations above 100 μM; this effect was more pronounced in myo−/− mice. DEA‐NONOate reduced Fc in preparations from myo−/− mice to a larger extent than those from WT mice. DETA‐NONOate reduced Fc in preparations from myo−/− but not from WT mice. Pre‐incubation with an inhibitor of the soluble guanylyl cyclase (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one; 100 μM) prevented the effects of SNAP, DEA‐NONOate and DETA‐NONOate on Fc in myo−/− mice. It is suggested that, in physiological conditions, myoglobin acts as intracellular scavenger preventing NO from reaching its intracellular receptors in cardiomyocytes, whereas, in myoglobin‐deficient conditions, NO is able to reduce contractility via activation of the soluble guanylyl cyclase/cyclic GMP pathway. British Journal of Pharmacology (2002) 136, 415–420; doi:10.1038/sj.bjp.0704740
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704740