Myoglobin: A scavenger of bioactive NO

The present study explored the role of myoglobin (Mb) in cardiac NO homeost asis and its functional relevance by employing isolated hearts of wild-type (WT) and myoglobin knockout mice,H-1 NMR spectroscopy was used to measure directly the conversion of oxygenated Mb (MbO(2)) to metmyoglobin (metMb) b y reaction with NO. NO was applied intracoronarily (5 nM to 25 muM), or its endogenous production was stimulated with bradykinin (Bk; 10 nM to 2 muM). We found that infusion of authentic NO solutions dose-dependently (greater than or equal to2.5 muM NO) increased metMb formation in WT hearts that wa s rapidly reversible on cessation of NO infusion, Likewise, Bk-induced rele ase of NO was associated with significant metMb formation in the WT(greater than or equal to1 muM Bk). Hearts lacking Mb reacted more sensitively to i nfused NO in that vasodilatation and the cardiodepressant actions of NO wer e more pronounced, Similar results were obtained with Bk. The lower sensiti vity of WT hearts to changes in NO concentration fits well with the hypothe sis that in the presence of Mb, a continuous degradation of NO takes place by reaction of MbO(2) + NO to metMb + NO3- thereby effectively reducing cyt osolic NO concentration. This breakdown protects myocytic cytochromes again st transient rises in cytosolic NO. Regeneration of metMb by metMb reductas e to Mb and subsequent association with O-2 leads to reformation of MbO(2) available for another NO degradation cycle. Our data indicate that this cyc le is crucial in the breakdown of NO and substantially determines the dose- response curve of the NO effects on coronary blood flow and cardiac contrac tility.