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Effects of nitric oxide donors on cardiac contractility in wild‐type and myoglobin‐deficient mice
Author(s) -
Wegener J W,
Gödecke A,
Schrader J,
Nawrath H
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704740
Subject(s) - nitric oxide , contractility , snap , myoglobin , soluble guanylyl cyclase , chemistry , nitrosylation , medicine , intracellular , endocrinology , sodium nitroprusside , contraction (grammar) , biochemistry , biology , guanylate cyclase , computer graphics (images) , computer science
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 (F c ) were studied in atrial and ventricular muscle strips obtained from wild‐type (WT) and myoglobin‐deficient (myo −/− ) mice. SNAP slightly reduced F c in preparations from WT mice at concentrations above 100 μ M ; this effect was more pronounced in myo −/− mice. DEA‐NONOate reduced F c in preparations from myo −/− mice to a larger extent than those from WT mice. DETA‐NONOate reduced F c in preparations from myo −/− but not from WT mice. Pre‐incubation with an inhibitor of the soluble guanylyl cyclase (1 H ‐[1,2,4]oxadiazolo[4,3‐ a ]quinoxalin‐1‐one; 100 μ M ) prevented the effects of SNAP, DEA‐NONOate and DETA‐NONOate on F c 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