Role of myoglobin as a scavenger of cellular NO in myocardium.
Recent studies have detected a (1)H nuclear magnetic resonance (NMR) reporter signal of metmyoglobin (metMb) during bradykinin stimulation of an isolated mouse heart. The observation has led to the hypothesis that Mb reacts with cellular nitric oxide (NO). However, the hypothesis depends on an unequivocal detection of metMb signals in vivo. In solution, nitrite oxidization of Mb produces a characteristic set of paramagnetically shifted (1)H NMR signals. In the upfield spectral region, MbO(2) and MbCO exhibit the gammaCH(3) Val E11 signals at -2.8 and -2.4 ppm, respectively. In the same spectral region, nitrite oxidation of Mb produces a set of signals at -3.7 and -4.7 ppm at 35 degrees C. Previous studies have confirmed the visibility of metMb signals in perfused rat myocardium. With bradykinin infusion, perfusion pressure and rate-pressure product decrease, consistent with endogenous NO formation. However, neither myocardial O(2) consumption nor high-energy phosphate levels, as reflected in the (31)P NMR signals, show any significant change. Bradykinin still triggers a similar physiological response even in the presence of CO that is sufficient to inhibit 86% Mb. In all cases, the (1)H NMR spectra from perfused rat myocardium reveal no metMb signals. The results suggest that bradykinin-induced NO does not interact significantly with cellular Mb to produce an NMR-detectable quantity of metMb in the perfused rat myocardium. As a consequence, the experiments cannot confirm the intriguing proposal that Mb acts as a cellular NO scavenger.
Kreutzer
Ulrike
U
Dept. of Biological Chemistry, Univ. of California, Davis, CA 95616-8635, USA.
Jue
Thomas
T
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D009211:Myoglobin; D009569:Nitric Oxide; D001920:Bradykinin